CN104081206B - 标记的hsp90抑制剂的用途 - Google Patents
标记的hsp90抑制剂的用途 Download PDFInfo
- Publication number
- CN104081206B CN104081206B CN201280040606.7A CN201280040606A CN104081206B CN 104081206 B CN104081206 B CN 104081206B CN 201280040606 A CN201280040606 A CN 201280040606A CN 104081206 B CN104081206 B CN 104081206B
- Authority
- CN
- China
- Prior art keywords
- hsp90
- tumour
- cell
- hsp90 inhibitor
- inhibitor
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
- 239000003481 heat shock protein 90 inhibitor Substances 0.000 title claims description 334
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 903
- 101710113864 Heat shock protein 90 Proteins 0.000 claims abstract description 602
- 102100034051 Heat shock protein HSP 90-alpha Human genes 0.000 claims abstract description 601
- 238000002560 therapeutic procedure Methods 0.000 claims abstract description 139
- 210000004881 tumor cell Anatomy 0.000 claims abstract description 85
- 238000005259 measurement Methods 0.000 claims abstract description 72
- 238000006243 chemical reaction Methods 0.000 claims abstract description 44
- 210000004027 cell Anatomy 0.000 claims description 469
- 201000011510 cancer Diseases 0.000 claims description 173
- 239000007850 fluorescent dye Substances 0.000 claims description 58
- 238000001215 fluorescent labelling Methods 0.000 claims description 58
- 208000032791 BCR-ABL1 positive chronic myelogenous leukemia Diseases 0.000 claims description 49
- 208000010833 Chronic myeloid leukaemia Diseases 0.000 claims description 47
- 239000008280 blood Substances 0.000 claims description 42
- 210000004369 blood Anatomy 0.000 claims description 41
- 210000004698 lymphocyte Anatomy 0.000 claims description 41
- 238000000684 flow cytometry Methods 0.000 claims description 30
- 208000032839 leukemia Diseases 0.000 claims description 28
- SUPVGFZUWFMATN-UHFFFAOYSA-N zelavespib Chemical compound N1=CN=C2N(CCCNC(C)C)C(SC=3C(=CC=4OCOC=4C=3)I)=NC2=C1N SUPVGFZUWFMATN-UHFFFAOYSA-N 0.000 claims description 24
- 201000005787 hematologic cancer Diseases 0.000 claims description 13
- 230000008823 permeabilization Effects 0.000 claims description 5
- 208000033761 Myelogenous Chronic BCR-ABL Positive Leukemia Diseases 0.000 claims description 4
- 230000006378 damage Effects 0.000 claims description 3
- 125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 claims description 3
- 230000008961 swelling Effects 0.000 claims 1
- 230000000711 cancerogenic effect Effects 0.000 abstract description 120
- 231100000315 carcinogenic Toxicity 0.000 abstract description 120
- 150000001875 compounds Chemical class 0.000 abstract description 100
- 230000000694 effects Effects 0.000 abstract description 55
- 239000000463 material Substances 0.000 abstract description 53
- 108010029477 STAT5 Transcription Factor Proteins 0.000 abstract description 43
- 102000001712 STAT5 Transcription Factor Human genes 0.000 abstract description 42
- 230000014509 gene expression Effects 0.000 abstract description 37
- WEVYNIUIFUYDGI-UHFFFAOYSA-N 3-[6-[4-(trifluoromethoxy)anilino]-4-pyrimidinyl]benzamide Chemical group NC(=O)C1=CC=CC(C=2N=CN=C(NC=3C=CC(OC(F)(F)F)=CC=3)C=2)=C1 WEVYNIUIFUYDGI-UHFFFAOYSA-N 0.000 abstract description 35
- 230000003211 malignant effect Effects 0.000 abstract description 34
- 230000004913 activation Effects 0.000 abstract description 22
- 239000000203 mixture Substances 0.000 abstract description 16
- 239000000090 biomarker Substances 0.000 abstract description 15
- 230000019491 signal transduction Effects 0.000 abstract description 11
- 230000035772 mutation Effects 0.000 abstract description 10
- 101001012157 Homo sapiens Receptor tyrosine-protein kinase erbB-2 Proteins 0.000 abstract description 9
- 102100030086 Receptor tyrosine-protein kinase erbB-2 Human genes 0.000 abstract description 9
- 230000002159 abnormal effect Effects 0.000 abstract description 9
- 102100021631 B-cell lymphoma 6 protein Human genes 0.000 abstract description 3
- 101000971234 Homo sapiens B-cell lymphoma 6 protein Proteins 0.000 abstract description 3
- 230000004637 cellular stress Effects 0.000 abstract description 3
- 108020001507 fusion proteins Proteins 0.000 abstract description 3
- 102000037865 fusion proteins Human genes 0.000 abstract description 3
- 230000002350 accommodative effect Effects 0.000 abstract description 2
- 238000000034 method Methods 0.000 description 115
- 239000003814 drug Substances 0.000 description 111
- 239000000523 sample Substances 0.000 description 109
- 108090000623 proteins and genes Proteins 0.000 description 106
- 102000004169 proteins and genes Human genes 0.000 description 104
- 235000018102 proteins Nutrition 0.000 description 103
- 238000004458 analytical method Methods 0.000 description 88
- 238000011282 treatment Methods 0.000 description 88
- 239000003112 inhibitor Substances 0.000 description 83
- 239000011324 bead Substances 0.000 description 81
- 235000020958 biotin Nutrition 0.000 description 79
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 64
- 238000005266 casting Methods 0.000 description 55
- 230000009102 absorption Effects 0.000 description 49
- 238000010521 absorption reaction Methods 0.000 description 49
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 46
- 201000010099 disease Diseases 0.000 description 43
- 208000031261 Acute myeloid leukaemia Diseases 0.000 description 39
- 239000011616 biotin Substances 0.000 description 34
- 229960002685 biotin Drugs 0.000 description 34
- 210000001109 blastomere Anatomy 0.000 description 34
- 239000007924 injection Substances 0.000 description 33
- 238000002347 injection Methods 0.000 description 33
- 230000008859 change Effects 0.000 description 30
- 210000001519 tissue Anatomy 0.000 description 30
- 241000699666 Mus <mouse, genus> Species 0.000 description 29
- -1 sulfonic acid chlorides Chemical class 0.000 description 29
- 102100031573 Hematopoietic progenitor cell antigen CD34 Human genes 0.000 description 27
- 101000777663 Homo sapiens Hematopoietic progenitor cell antigen CD34 Proteins 0.000 description 27
- 230000015572 biosynthetic process Effects 0.000 description 27
- 206010006187 Breast cancer Diseases 0.000 description 26
- 229940079593 drug Drugs 0.000 description 26
- 208000026310 Breast neoplasm Diseases 0.000 description 25
- 206010061902 Pancreatic neoplasm Diseases 0.000 description 25
- 239000003795 chemical substances by application Substances 0.000 description 25
- 230000001629 suppression Effects 0.000 description 25
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 description 24
- 238000003786 synthesis reaction Methods 0.000 description 24
- 239000012071 phase Substances 0.000 description 23
- XGWFJBFNAQHLEF-UHFFFAOYSA-N 9-anthroic acid Chemical compound C1=CC=C2C(C(=O)O)=C(C=CC=C3)C3=CC2=C1 XGWFJBFNAQHLEF-UHFFFAOYSA-N 0.000 description 22
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 22
- 238000002474 experimental method Methods 0.000 description 22
- 239000007788 liquid Substances 0.000 description 22
- ZCYVEMRRCGMTRW-OIOBTWANSA-N [124I] Chemical compound [124I] ZCYVEMRRCGMTRW-OIOBTWANSA-N 0.000 description 21
- 238000001994 activation Methods 0.000 description 21
- 239000002585 base Substances 0.000 description 21
- 239000000700 radioactive tracer Substances 0.000 description 21
- 238000011160 research Methods 0.000 description 21
- 239000000975 dye Substances 0.000 description 20
- 230000008569 process Effects 0.000 description 20
- 101000738771 Homo sapiens Receptor-type tyrosine-protein phosphatase C Proteins 0.000 description 19
- 102100037422 Receptor-type tyrosine-protein phosphatase C Human genes 0.000 description 19
- 238000002372 labelling Methods 0.000 description 19
- OTMSDBZUPAUEDD-UHFFFAOYSA-N Ethane Chemical compound CC OTMSDBZUPAUEDD-UHFFFAOYSA-N 0.000 description 18
- 230000001419 dependent effect Effects 0.000 description 18
- 239000000284 extract Substances 0.000 description 18
- 210000003205 muscle Anatomy 0.000 description 18
- 230000004083 survival effect Effects 0.000 description 18
- 230000006907 apoptotic process Effects 0.000 description 17
- 238000001990 intravenous administration Methods 0.000 description 17
- 238000013461 design Methods 0.000 description 16
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 15
- 238000003384 imaging method Methods 0.000 description 15
- 230000026731 phosphorylation Effects 0.000 description 15
- 238000006366 phosphorylation reaction Methods 0.000 description 15
- QLNJFJADRCOGBJ-UHFFFAOYSA-N propionamide Chemical compound CCC(N)=O QLNJFJADRCOGBJ-UHFFFAOYSA-N 0.000 description 15
- 229940080818 propionamide Drugs 0.000 description 15
- 238000012879 PET imaging Methods 0.000 description 13
- 210000001165 lymph node Anatomy 0.000 description 13
- 230000003442 weekly effect Effects 0.000 description 13
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 12
- 210000000265 leukocyte Anatomy 0.000 description 12
- 238000001294 liquid chromatography-tandem mass spectrometry Methods 0.000 description 12
- 210000004072 lung Anatomy 0.000 description 12
- 208000020816 lung neoplasm Diseases 0.000 description 12
- 210000002381 plasma Anatomy 0.000 description 12
- 230000009467 reduction Effects 0.000 description 12
- 238000011287 therapeutic dose Methods 0.000 description 12
- 230000034994 death Effects 0.000 description 11
- 210000004700 fetal blood Anatomy 0.000 description 11
- 239000006166 lysate Substances 0.000 description 11
- 238000002360 preparation method Methods 0.000 description 11
- 239000000126 substance Substances 0.000 description 11
- 238000012360 testing method Methods 0.000 description 11
- 230000035899 viability Effects 0.000 description 11
- 238000001262 western blot Methods 0.000 description 11
- 238000013459 approach Methods 0.000 description 10
- 230000001413 cellular effect Effects 0.000 description 10
- 238000011161 development Methods 0.000 description 10
- 230000018109 developmental process Effects 0.000 description 10
- 230000006870 function Effects 0.000 description 10
- 238000001727 in vivo Methods 0.000 description 10
- 230000003834 intracellular effect Effects 0.000 description 10
- 238000007912 intraperitoneal administration Methods 0.000 description 10
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 10
- 238000012544 monitoring process Methods 0.000 description 10
- 208000008443 pancreatic carcinoma Diseases 0.000 description 10
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 10
- 230000004044 response Effects 0.000 description 10
- 108700012813 7-aminoactinomycin D Proteins 0.000 description 9
- YXHLJMWYDTXDHS-IRFLANFNSA-N 7-aminoactinomycin D Chemical compound C[C@H]1OC(=O)[C@H](C(C)C)N(C)C(=O)CN(C)C(=O)[C@@H]2CCCN2C(=O)[C@@H](C(C)C)NC(=O)[C@H]1NC(=O)C1=C(N)C(=O)C(C)=C2OC(C(C)=C(N)C=C3C(=O)N[C@@H]4C(=O)N[C@@H](C(N5CCC[C@H]5C(=O)N(C)CC(=O)N(C)[C@@H](C(C)C)C(=O)O[C@@H]4C)=O)C(C)C)=C3N=C21 YXHLJMWYDTXDHS-IRFLANFNSA-N 0.000 description 9
- 208000003569 Central serous chorioretinopathy Diseases 0.000 description 9
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 9
- 241001465754 Metazoa Species 0.000 description 9
- 108091000080 Phosphotransferase Proteins 0.000 description 9
- 208000005718 Stomach Neoplasms Diseases 0.000 description 9
- 210000000988 bone and bone Anatomy 0.000 description 9
- 230000001684 chronic effect Effects 0.000 description 9
- 206010017758 gastric cancer Diseases 0.000 description 9
- 230000036541 health Effects 0.000 description 9
- 201000005202 lung cancer Diseases 0.000 description 9
- 230000003285 pharmacodynamic effect Effects 0.000 description 9
- 102000020233 phosphotransferase Human genes 0.000 description 9
- 230000002829 reductive effect Effects 0.000 description 9
- 230000035945 sensitivity Effects 0.000 description 9
- 210000000130 stem cell Anatomy 0.000 description 9
- 201000011549 stomach cancer Diseases 0.000 description 9
- 230000008685 targeting Effects 0.000 description 9
- 230000001988 toxicity Effects 0.000 description 9
- 231100000419 toxicity Toxicity 0.000 description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 9
- FWBHETKCLVMNFS-UHFFFAOYSA-N 4',6-Diamino-2-phenylindol Chemical compound C1=CC(C(=N)N)=CC=C1C1=CC2=CC=C(C(N)=N)C=C2N1 FWBHETKCLVMNFS-UHFFFAOYSA-N 0.000 description 8
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 8
- 108090000672 Annexin A5 Proteins 0.000 description 8
- 102000004121 Annexin A5 Human genes 0.000 description 8
- 208000005443 Circulating Neoplastic Cells Diseases 0.000 description 8
- 108010090804 Streptavidin Proteins 0.000 description 8
- 230000035508 accumulation Effects 0.000 description 8
- 238000009825 accumulation Methods 0.000 description 8
- 230000000259 anti-tumor effect Effects 0.000 description 8
- 230000027455 binding Effects 0.000 description 8
- 238000009739 binding Methods 0.000 description 8
- 230000033228 biological regulation Effects 0.000 description 8
- 238000004043 dyeing Methods 0.000 description 8
- 230000003993 interaction Effects 0.000 description 8
- 229910052740 iodine Inorganic materials 0.000 description 8
- 238000012423 maintenance Methods 0.000 description 8
- 210000000056 organ Anatomy 0.000 description 8
- 229920000371 poly(diallyldimethylammonium chloride) polymer Polymers 0.000 description 8
- 238000012636 positron electron tomography Methods 0.000 description 8
- 238000004393 prognosis Methods 0.000 description 8
- 150000003839 salts Chemical class 0.000 description 8
- RRSNDVCODIMOFX-MPKOGUQCSA-N Fc1c(Cl)cccc1[C@H]1[C@@H](NC2(CCCCC2)[C@@]11C(=O)Nc2cc(Cl)ccc12)C(=O)Nc1ccc(cc1)C(=O)NCCCCCc1cccc2C(=O)N(Cc12)C1CCC(=O)NC1=O Chemical compound Fc1c(Cl)cccc1[C@H]1[C@@H](NC2(CCCCC2)[C@@]11C(=O)Nc2cc(Cl)ccc12)C(=O)Nc1ccc(cc1)C(=O)NCCCCCc1cccc2C(=O)N(Cc12)C1CCC(=O)NC1=O RRSNDVCODIMOFX-MPKOGUQCSA-N 0.000 description 7
- 102100025210 Histone-arginine methyltransferase CARM1 Human genes 0.000 description 7
- 206010060862 Prostate cancer Diseases 0.000 description 7
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 7
- 108091008611 Protein Kinase B Proteins 0.000 description 7
- 150000001412 amines Chemical class 0.000 description 7
- 210000003719 b-lymphocyte Anatomy 0.000 description 7
- 238000001574 biopsy Methods 0.000 description 7
- 210000004556 brain Anatomy 0.000 description 7
- 108010030886 coactivator-associated arginine methyltransferase 1 Proteins 0.000 description 7
- 238000012377 drug delivery Methods 0.000 description 7
- GNBHRKFJIUUOQI-UHFFFAOYSA-N fluorescein Chemical compound O1C(=O)C2=CC=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 GNBHRKFJIUUOQI-UHFFFAOYSA-N 0.000 description 7
- 229910052739 hydrogen Inorganic materials 0.000 description 7
- 239000001257 hydrogen Substances 0.000 description 7
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 7
- 210000000936 intestine Anatomy 0.000 description 7
- 230000003902 lesion Effects 0.000 description 7
- 210000004185 liver Anatomy 0.000 description 7
- 208000019420 lymphoid neoplasm Diseases 0.000 description 7
- 231100000682 maximum tolerated dose Toxicity 0.000 description 7
- 238000000746 purification Methods 0.000 description 7
- 210000002784 stomach Anatomy 0.000 description 7
- 239000006228 supernatant Substances 0.000 description 7
- 230000035897 transcription Effects 0.000 description 7
- 238000013518 transcription Methods 0.000 description 7
- KKVYYGGCHJGEFJ-UHFFFAOYSA-N 1-n-(4-chlorophenyl)-6-methyl-5-n-[3-(7h-purin-6-yl)pyridin-2-yl]isoquinoline-1,5-diamine Chemical class N=1C=CC2=C(NC=3C(=CC=CN=3)C=3C=4N=CNC=4N=CN=3)C(C)=CC=C2C=1NC1=CC=C(Cl)C=C1 KKVYYGGCHJGEFJ-UHFFFAOYSA-N 0.000 description 6
- KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical group N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 6
- 208000007860 Anus Neoplasms Diseases 0.000 description 6
- 206010004146 Basal cell carcinoma Diseases 0.000 description 6
- 208000003174 Brain Neoplasms Diseases 0.000 description 6
- 108010037003 Buserelin Proteins 0.000 description 6
- 101100507655 Canis lupus familiaris HSPA1 gene Proteins 0.000 description 6
- 208000017897 Carcinoma of esophagus Diseases 0.000 description 6
- 206010014759 Endometrial neoplasm Diseases 0.000 description 6
- 208000000461 Esophageal Neoplasms Diseases 0.000 description 6
- 208000032612 Glial tumor Diseases 0.000 description 6
- 206010018338 Glioma Diseases 0.000 description 6
- JTPUMZTWMWIVPA-UHFFFAOYSA-O Isopropamide Chemical compound C=1C=CC=CC=1C(C(N)=O)(CC[N+](C)(C(C)C)C(C)C)C1=CC=CC=C1 JTPUMZTWMWIVPA-UHFFFAOYSA-O 0.000 description 6
- 201000007224 Myeloproliferative neoplasm Diseases 0.000 description 6
- 206010029260 Neuroblastoma Diseases 0.000 description 6
- 241000255964 Pieridae Species 0.000 description 6
- 102100033479 RAF proto-oncogene serine/threonine-protein kinase Human genes 0.000 description 6
- 101710141955 RAF proto-oncogene serine/threonine-protein kinase Proteins 0.000 description 6
- 108010065917 TOR Serine-Threonine Kinases Proteins 0.000 description 6
- 102000013530 TOR Serine-Threonine Kinases Human genes 0.000 description 6
- 208000024770 Thyroid neoplasm Diseases 0.000 description 6
- 125000000217 alkyl group Chemical group 0.000 description 6
- 150000001408 amides Chemical class 0.000 description 6
- 201000011165 anus cancer Diseases 0.000 description 6
- 230000008901 benefit Effects 0.000 description 6
- 210000000601 blood cell Anatomy 0.000 description 6
- 229960002719 buserelin Drugs 0.000 description 6
- 208000009060 clear cell adenocarcinoma Diseases 0.000 description 6
- 238000001514 detection method Methods 0.000 description 6
- ATUOYWHBWRKTHZ-UHFFFAOYSA-N dimethylmethane Natural products CCC ATUOYWHBWRKTHZ-UHFFFAOYSA-N 0.000 description 6
- 201000003914 endometrial carcinoma Diseases 0.000 description 6
- 230000002349 favourable effect Effects 0.000 description 6
- 201000003444 follicular lymphoma Diseases 0.000 description 6
- 201000010175 gallbladder cancer Diseases 0.000 description 6
- 229910052736 halogen Inorganic materials 0.000 description 6
- 150000002367 halogens Chemical class 0.000 description 6
- 208000024200 hematopoietic and lymphoid system neoplasm Diseases 0.000 description 6
- 238000000338 in vitro Methods 0.000 description 6
- 239000011630 iodine Substances 0.000 description 6
- WFKAJVHLWXSISD-UHFFFAOYSA-N isobutyramide Chemical compound CC(C)C(N)=O WFKAJVHLWXSISD-UHFFFAOYSA-N 0.000 description 6
- 229960001737 isopropamide Drugs 0.000 description 6
- 201000007270 liver cancer Diseases 0.000 description 6
- 208000014018 liver neoplasm Diseases 0.000 description 6
- 208000002154 non-small cell lung carcinoma Diseases 0.000 description 6
- XIPFMBOWZXULIA-UHFFFAOYSA-N pivalamide Chemical compound CC(C)(C)C(N)=O XIPFMBOWZXULIA-UHFFFAOYSA-N 0.000 description 6
- 239000001294 propane Substances 0.000 description 6
- 150000003384 small molecules Chemical class 0.000 description 6
- 239000000243 solution Substances 0.000 description 6
- 229940124530 sulfonamide Drugs 0.000 description 6
- 238000002626 targeted therapy Methods 0.000 description 6
- 229940124597 therapeutic agent Drugs 0.000 description 6
- 230000001225 therapeutic effect Effects 0.000 description 6
- 201000002510 thyroid cancer Diseases 0.000 description 6
- 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 description 6
- SWDZPNJZKUGIIH-QQTULTPQSA-N (5z)-n-ethyl-5-(4-hydroxy-6-oxo-3-propan-2-ylcyclohexa-2,4-dien-1-ylidene)-4-[4-(morpholin-4-ylmethyl)phenyl]-2h-1,2-oxazole-3-carboxamide Chemical compound O1NC(C(=O)NCC)=C(C=2C=CC(CN3CCOCC3)=CC=2)\C1=C1/C=C(C(C)C)C(O)=CC1=O SWDZPNJZKUGIIH-QQTULTPQSA-N 0.000 description 5
- 206010009944 Colon cancer Diseases 0.000 description 5
- 102000018651 Epithelial Cell Adhesion Molecule Human genes 0.000 description 5
- 108010066687 Epithelial Cell Adhesion Molecule Proteins 0.000 description 5
- 208000033776 Myeloid Acute Leukemia Diseases 0.000 description 5
- 102000002727 Protein Tyrosine Phosphatase Human genes 0.000 description 5
- 201000001531 bladder carcinoma Diseases 0.000 description 5
- 239000007853 buffer solution Substances 0.000 description 5
- 238000004364 calculation method Methods 0.000 description 5
- 239000013592 cell lysate Substances 0.000 description 5
- 208000019065 cervical carcinoma Diseases 0.000 description 5
- ZFVRYNYOPQZKDG-MQMHXKEQSA-N chembl560895 Chemical compound O=C1CC(C)(C)CC2=C1C(C(F)(F)F)=NN2C(C=1)=CC=C(C(N)=O)C=1N[C@H]1CC[C@H](O)CC1 ZFVRYNYOPQZKDG-MQMHXKEQSA-N 0.000 description 5
- 239000003153 chemical reaction reagent Substances 0.000 description 5
- 229940125782 compound 2 Drugs 0.000 description 5
- 230000030609 dephosphorylation Effects 0.000 description 5
- 238000006209 dephosphorylation reaction Methods 0.000 description 5
- 201000007487 gallbladder carcinoma Diseases 0.000 description 5
- 210000002216 heart Anatomy 0.000 description 5
- 238000003119 immunoblot Methods 0.000 description 5
- 230000001965 increasing effect Effects 0.000 description 5
- 229950005069 luminespib Drugs 0.000 description 5
- 230000014759 maintenance of location Effects 0.000 description 5
- 201000001441 melanoma Diseases 0.000 description 5
- 229910052760 oxygen Inorganic materials 0.000 description 5
- 201000002528 pancreatic cancer Diseases 0.000 description 5
- 238000012545 processing Methods 0.000 description 5
- 108020000494 protein-tyrosine phosphatase Proteins 0.000 description 5
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 5
- 238000012546 transfer Methods 0.000 description 5
- 208000010570 urinary bladder carcinoma Diseases 0.000 description 5
- 102100031585 ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 1 Human genes 0.000 description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 4
- 108020004414 DNA Proteins 0.000 description 4
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 4
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 4
- 206010017993 Gastrointestinal neoplasms Diseases 0.000 description 4
- 206010051066 Gastrointestinal stromal tumour Diseases 0.000 description 4
- 101000777636 Homo sapiens ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 1 Proteins 0.000 description 4
- 101000617830 Homo sapiens Sterol O-acyltransferase 1 Proteins 0.000 description 4
- 241000699670 Mus sp. Species 0.000 description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
- 206010035226 Plasma cell myeloma Diseases 0.000 description 4
- 239000004698 Polyethylene Substances 0.000 description 4
- 102100021993 Sterol O-acyltransferase 1 Human genes 0.000 description 4
- 101000697584 Streptomyces lavendulae Streptothricin acetyltransferase Proteins 0.000 description 4
- 239000003513 alkali Substances 0.000 description 4
- 150000001615 biotins Chemical class 0.000 description 4
- 230000037396 body weight Effects 0.000 description 4
- 210000000621 bronchi Anatomy 0.000 description 4
- 230000003833 cell viability Effects 0.000 description 4
- 238000009388 chemical precipitation Methods 0.000 description 4
- 238000010586 diagram Methods 0.000 description 4
- 238000009826 distribution Methods 0.000 description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 4
- 210000002950 fibroblast Anatomy 0.000 description 4
- 238000000799 fluorescence microscopy Methods 0.000 description 4
- 238000001943 fluorescence-activated cell sorting Methods 0.000 description 4
- 201000011243 gastrointestinal stromal tumor Diseases 0.000 description 4
- 239000000499 gel Substances 0.000 description 4
- 230000001900 immune effect Effects 0.000 description 4
- 230000002045 lasting effect Effects 0.000 description 4
- 210000002751 lymph Anatomy 0.000 description 4
- 230000007246 mechanism Effects 0.000 description 4
- 230000001394 metastastic effect Effects 0.000 description 4
- 206010061289 metastatic neoplasm Diseases 0.000 description 4
- 201000000050 myeloid neoplasm Diseases 0.000 description 4
- 229910052757 nitrogen Inorganic materials 0.000 description 4
- 239000013610 patient sample Substances 0.000 description 4
- 230000035699 permeability Effects 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- 230000002035 prolonged effect Effects 0.000 description 4
- 230000000306 recurrent effect Effects 0.000 description 4
- 210000000952 spleen Anatomy 0.000 description 4
- COIVODZMVVUETJ-UHFFFAOYSA-N sulforhodamine 101 Chemical compound OS(=O)(=O)C1=CC(S([O-])(=O)=O)=CC=C1C1=C(C=C2C3=C4CCCN3CCC2)C4=[O+]C2=C1C=C1CCCN3CCCC2=C13 COIVODZMVVUETJ-UHFFFAOYSA-N 0.000 description 4
- 229910052717 sulfur Inorganic materials 0.000 description 4
- 230000004614 tumor growth Effects 0.000 description 4
- 238000010176 18-FDG-positron emission tomography Methods 0.000 description 3
- ZCXUVYAZINUVJD-AHXZWLDOSA-N 2-deoxy-2-((18)F)fluoro-alpha-D-glucose Chemical compound OC[C@H]1O[C@H](O)[C@H]([18F])[C@@H](O)[C@@H]1O ZCXUVYAZINUVJD-AHXZWLDOSA-N 0.000 description 3
- LZKPMNCTFKUWIX-UHFFFAOYSA-N 2-methyl-n-propylpropane-1-sulfonamide Chemical class CCCNS(=O)(=O)CC(C)C LZKPMNCTFKUWIX-UHFFFAOYSA-N 0.000 description 3
- SCDDZPIYMIUTKB-UHFFFAOYSA-N 2-methyl-n-propylpropane-2-sulfinamide Chemical class CCCNS(=O)C(C)(C)C SCDDZPIYMIUTKB-UHFFFAOYSA-N 0.000 description 3
- FKOZPUORKCHONH-UHFFFAOYSA-N 2-methylpropane-1-sulfonic acid Chemical compound CC(C)CS(O)(=O)=O FKOZPUORKCHONH-UHFFFAOYSA-N 0.000 description 3
- DUWLIIPTRMQEAP-UHFFFAOYSA-N 2-methylpropane-2-sulfinic acid Chemical compound CC(C)(C)S(O)=O DUWLIIPTRMQEAP-UHFFFAOYSA-N 0.000 description 3
- XCJGLBWDZKLQCY-UHFFFAOYSA-N 2-methylpropane-2-sulfonic acid Chemical compound CC(C)(C)S(O)(=O)=O XCJGLBWDZKLQCY-UHFFFAOYSA-N 0.000 description 3
- IGHBXJSNZCFXNK-UHFFFAOYSA-N 4-chloro-7-nitrobenzofurazan Chemical compound [O-][N+](=O)C1=CC=C(Cl)C2=NON=C12 IGHBXJSNZCFXNK-UHFFFAOYSA-N 0.000 description 3
- 208000019838 Blood disease Diseases 0.000 description 3
- 101710163595 Chaperone protein DnaK Proteins 0.000 description 3
- 208000001333 Colorectal Neoplasms Diseases 0.000 description 3
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
- 241000282326 Felis catus Species 0.000 description 3
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 description 3
- JRZJKWGQFNTSRN-UHFFFAOYSA-N Geldanamycin Natural products C1C(C)CC(OC)C(O)C(C)C=C(C)C(OC(N)=O)C(OC)CCC=C(C)C(=O)NC2=CC(=O)C(OC)=C1C2=O JRZJKWGQFNTSRN-UHFFFAOYSA-N 0.000 description 3
- 101710178376 Heat shock 70 kDa protein Proteins 0.000 description 3
- 101710152018 Heat shock cognate 70 kDa protein Proteins 0.000 description 3
- 206010020751 Hypersensitivity Diseases 0.000 description 3
- ZCYVEMRRCGMTRW-AHCXROLUSA-N Iodine-123 Chemical compound [123I] ZCYVEMRRCGMTRW-AHCXROLUSA-N 0.000 description 3
- 239000005517 L01XE01 - Imatinib Substances 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 101100381978 Mus musculus Braf gene Proteins 0.000 description 3
- NQTADLQHYWFPDB-UHFFFAOYSA-N N-Hydroxysuccinimide Chemical compound ON1C(=O)CCC1=O NQTADLQHYWFPDB-UHFFFAOYSA-N 0.000 description 3
- ZRKWMRDKSOPRRS-UHFFFAOYSA-N N-Methyl-N-nitrosourea Chemical compound O=NN(C)C(N)=O ZRKWMRDKSOPRRS-UHFFFAOYSA-N 0.000 description 3
- PMDCZENCAXMSOU-UHFFFAOYSA-N N-ethylacetamide Chemical class CCNC(C)=O PMDCZENCAXMSOU-UHFFFAOYSA-N 0.000 description 3
- 108010058765 Oncogene Protein pp60(v-src) Proteins 0.000 description 3
- 206010033128 Ovarian cancer Diseases 0.000 description 3
- 206010061535 Ovarian neoplasm Diseases 0.000 description 3
- 102000004160 Phosphoric Monoester Hydrolases Human genes 0.000 description 3
- 108090000608 Phosphoric Monoester Hydrolases Proteins 0.000 description 3
- 108060006706 SRC Proteins 0.000 description 3
- 102000001332 SRC Human genes 0.000 description 3
- 108010017324 STAT3 Transcription Factor Proteins 0.000 description 3
- 102100024040 Signal transducer and activator of transcription 3 Human genes 0.000 description 3
- 206010041067 Small cell lung cancer Diseases 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 230000009286 beneficial effect Effects 0.000 description 3
- CUWODFFVMXJOKD-UVLQAERKSA-N buserelin Chemical compound CCNC(=O)[C@@H]1CCCN1C(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](COC(C)(C)C)NC(=O)[C@@H](NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H]1NC(=O)CC1)CC1=CC=C(O)C=C1 CUWODFFVMXJOKD-UVLQAERKSA-N 0.000 description 3
- 229910052799 carbon Inorganic materials 0.000 description 3
- 230000015556 catabolic process Effects 0.000 description 3
- 230000010261 cell growth Effects 0.000 description 3
- 230000004087 circulation Effects 0.000 description 3
- 229940124579 cold medicine Drugs 0.000 description 3
- 210000001072 colon Anatomy 0.000 description 3
- 229940126214 compound 3 Drugs 0.000 description 3
- 238000006731 degradation reaction Methods 0.000 description 3
- 239000000539 dimer Substances 0.000 description 3
- 231100000673 dose–response relationship Toxicity 0.000 description 3
- 230000000857 drug effect Effects 0.000 description 3
- 230000008482 dysregulation Effects 0.000 description 3
- 238000005516 engineering process Methods 0.000 description 3
- 150000002148 esters Chemical class 0.000 description 3
- CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 3
- 238000011156 evaluation Methods 0.000 description 3
- 229910052731 fluorine Inorganic materials 0.000 description 3
- 239000011737 fluorine Substances 0.000 description 3
- QTQAWLPCGQOSGP-GBTDJJJQSA-N geldanamycin Chemical compound N1C(=O)\C(C)=C/C=C\[C@@H](OC)[C@H](OC(N)=O)\C(C)=C/[C@@H](C)[C@@H](O)[C@H](OC)C[C@@H](C)CC2=C(OC)C(=O)C=C1C2=O QTQAWLPCGQOSGP-GBTDJJJQSA-N 0.000 description 3
- 230000035876 healing Effects 0.000 description 3
- 208000014951 hematologic disease Diseases 0.000 description 3
- 238000004128 high performance liquid chromatography Methods 0.000 description 3
- 210000004408 hybridoma Anatomy 0.000 description 3
- 230000009610 hypersensitivity Effects 0.000 description 3
- 238000001114 immunoprecipitation Methods 0.000 description 3
- XMBWDFGMSWQBCA-OIOBTWANSA-N iodane Chemical compound [124IH] XMBWDFGMSWQBCA-OIOBTWANSA-N 0.000 description 3
- NNPPMTNAJDCUHE-UHFFFAOYSA-N isobutane Chemical compound CC(C)C NNPPMTNAJDCUHE-UHFFFAOYSA-N 0.000 description 3
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 3
- 229940047889 isobutyramide Drugs 0.000 description 3
- 210000003734 kidney Anatomy 0.000 description 3
- 239000003446 ligand Substances 0.000 description 3
- 210000001616 monocyte Anatomy 0.000 description 3
- ICMYVGUJSCZEMG-UHFFFAOYSA-N n-ethyl-2,2-dimethylpropanamide Chemical class CCNC(=O)C(C)(C)C ICMYVGUJSCZEMG-UHFFFAOYSA-N 0.000 description 3
- WLQCOYYCNXROKF-UHFFFAOYSA-N n-ethylcyclopropanecarboxamide Chemical class CCNC(=O)C1CC1 WLQCOYYCNXROKF-UHFFFAOYSA-N 0.000 description 3
- KERBAAIBDHEFDD-UHFFFAOYSA-N n-ethylformamide Chemical class CCNC=O KERBAAIBDHEFDD-UHFFFAOYSA-N 0.000 description 3
- IBMVWPYCKNHSRA-UHFFFAOYSA-N n-propylethanesulfonamide Chemical class CCCNS(=O)(=O)CC IBMVWPYCKNHSRA-UHFFFAOYSA-N 0.000 description 3
- OOPVMFMDPJFBFN-UHFFFAOYSA-N n-propylpropane-2-sulfonamide Chemical class CCCNS(=O)(=O)C(C)C OOPVMFMDPJFBFN-UHFFFAOYSA-N 0.000 description 3
- 230000009871 nonspecific binding Effects 0.000 description 3
- 210000000496 pancreas Anatomy 0.000 description 3
- 230000035515 penetration Effects 0.000 description 3
- 210000005259 peripheral blood Anatomy 0.000 description 3
- 239000011886 peripheral blood Substances 0.000 description 3
- 230000000144 pharmacologic effect Effects 0.000 description 3
- 231100000614 poison Toxicity 0.000 description 3
- 230000007096 poisonous effect Effects 0.000 description 3
- 229920000151 polyglycol Polymers 0.000 description 3
- 239000010695 polyglycol Substances 0.000 description 3
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 3
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 3
- WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical class CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 description 3
- 238000000926 separation method Methods 0.000 description 3
- 238000004088 simulation Methods 0.000 description 3
- 238000002603 single-photon emission computed tomography Methods 0.000 description 3
- 150000003456 sulfonamides Chemical class 0.000 description 3
- 238000001356 surgical procedure Methods 0.000 description 3
- AYUNIORJHRXIBJ-TXHRRWQRSA-N tanespimycin Chemical compound N1C(=O)\C(C)=C\C=C/[C@H](OC)[C@@H](OC(N)=O)\C(C)=C\[C@H](C)[C@@H](O)[C@@H](OC)C[C@H](C)CC2=C(NCC=C)C(=O)C=C1C2=O AYUNIORJHRXIBJ-TXHRRWQRSA-N 0.000 description 3
- 230000002123 temporal effect Effects 0.000 description 3
- 210000001685 thyroid gland Anatomy 0.000 description 3
- 231100000027 toxicology Toxicity 0.000 description 3
- 238000005406 washing Methods 0.000 description 3
- PNDPGZBMCMUPRI-HVTJNCQCSA-N 10043-66-0 Chemical compound [131I][131I] PNDPGZBMCMUPRI-HVTJNCQCSA-N 0.000 description 2
- RVJIQAYFTOPTKK-UHFFFAOYSA-N 2-[[6-(dimethylamino)-1,3-benzodioxol-5-yl]sulfanyl]-1-[2-(2,2-dimethylpropylamino)ethyl]imidazo[4,5-c]pyridin-4-amine Chemical compound N1=CC=C2N(CCNCC(C)(C)C)C(SC3=CC=4OCOC=4C=C3N(C)C)=NC2=C1N RVJIQAYFTOPTKK-UHFFFAOYSA-N 0.000 description 2
- YSUIQYOGTINQIN-UZFYAQMZSA-N 2-amino-9-[(1S,6R,8R,9S,10R,15R,17R,18R)-8-(6-aminopurin-9-yl)-9,18-difluoro-3,12-dihydroxy-3,12-bis(sulfanylidene)-2,4,7,11,13,16-hexaoxa-3lambda5,12lambda5-diphosphatricyclo[13.2.1.06,10]octadecan-17-yl]-1H-purin-6-one Chemical compound NC1=NC2=C(N=CN2[C@@H]2O[C@@H]3COP(S)(=O)O[C@@H]4[C@@H](COP(S)(=O)O[C@@H]2[C@@H]3F)O[C@H]([C@H]4F)N2C=NC3=C2N=CN=C3N)C(=O)N1 YSUIQYOGTINQIN-UZFYAQMZSA-N 0.000 description 2
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 description 2
- GAMYYCRTACQSBR-UHFFFAOYSA-N 4-azabenzimidazole Chemical compound C1=CC=C2NC=NC2=N1 GAMYYCRTACQSBR-UHFFFAOYSA-N 0.000 description 2
- 208000024893 Acute lymphoblastic leukemia Diseases 0.000 description 2
- 208000014697 Acute lymphocytic leukaemia Diseases 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- 102000004506 Blood Proteins Human genes 0.000 description 2
- 108010017384 Blood Proteins Proteins 0.000 description 2
- 206010061728 Bone lesion Diseases 0.000 description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- 102100029375 Crk-like protein Human genes 0.000 description 2
- 102100029721 DnaJ homolog subfamily B member 1 Human genes 0.000 description 2
- 206010073364 Ductal adenocarcinoma of pancreas Diseases 0.000 description 2
- 238000002965 ELISA Methods 0.000 description 2
- 241000196324 Embryophyta Species 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- RVAQIUULWULRNW-UHFFFAOYSA-N Ganetespib Chemical compound C1=C(O)C(C(C)C)=CC(C=2N(C(O)=NN=2)C=2C=C3C=CN(C)C3=CC=2)=C1O RVAQIUULWULRNW-UHFFFAOYSA-N 0.000 description 2
- 108010042283 HSP40 Heat-Shock Proteins Proteins 0.000 description 2
- 101000919315 Homo sapiens Crk-like protein Proteins 0.000 description 2
- 101001016865 Homo sapiens Heat shock protein HSP 90-alpha Proteins 0.000 description 2
- 101000839095 Homo sapiens Homeodomain-only protein Proteins 0.000 description 2
- 101000946889 Homo sapiens Monocyte differentiation antigen CD14 Proteins 0.000 description 2
- 101001030211 Homo sapiens Myc proto-oncogene protein Proteins 0.000 description 2
- 102000042838 JAK family Human genes 0.000 description 2
- 108091082332 JAK family Proteins 0.000 description 2
- 239000005551 L01XE03 - Erlotinib Substances 0.000 description 2
- 208000028018 Lymphocytic leukaemia Diseases 0.000 description 2
- 206010025323 Lymphomas Diseases 0.000 description 2
- XUMBMVFBXHLACL-UHFFFAOYSA-N Melanin Chemical compound O=C1C(=O)C(C2=CNC3=C(C(C(=O)C4=C32)=O)C)=C2C4=CNC2=C1C XUMBMVFBXHLACL-UHFFFAOYSA-N 0.000 description 2
- 102100035877 Monocyte differentiation antigen CD14 Human genes 0.000 description 2
- 238000000636 Northern blotting Methods 0.000 description 2
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 2
- 229920000776 Poly(Adenosine diphosphate-ribose) polymerase Polymers 0.000 description 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
- 208000006664 Precursor Cell Lymphoblastic Leukemia-Lymphoma Diseases 0.000 description 2
- 102000004022 Protein-Tyrosine Kinases Human genes 0.000 description 2
- 108090000412 Protein-Tyrosine Kinases Proteins 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- 102100033810 RAC-alpha serine/threonine-protein kinase Human genes 0.000 description 2
- 238000011579 SCID mouse model Methods 0.000 description 2
- 108091027967 Small hairpin RNA Proteins 0.000 description 2
- DPKHZNPWBDQZCN-UHFFFAOYSA-N acridine orange free base Chemical compound C1=CC(N(C)C)=CC2=NC3=CC(N(C)C)=CC=C3C=C21 DPKHZNPWBDQZCN-UHFFFAOYSA-N 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 125000002877 alkyl aryl group Chemical group 0.000 description 2
- 208000026935 allergic disease Diseases 0.000 description 2
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 2
- KUFRQPKVAWMTJO-LMZWQJSESA-N alvespimycin Chemical compound N1C(=O)\C(C)=C\C=C/[C@H](OC)[C@@H](OC(N)=O)\C(C)=C\[C@H](C)[C@@H](O)[C@@H](OC)C[C@H](C)CC2=C(NCCN(C)C)C(=O)C=C1C2=O KUFRQPKVAWMTJO-LMZWQJSESA-N 0.000 description 2
- 239000000427 antigen Substances 0.000 description 2
- 108091007433 antigens Proteins 0.000 description 2
- 102000036639 antigens Human genes 0.000 description 2
- 230000006399 behavior Effects 0.000 description 2
- DZBUGLKDJFMEHC-UHFFFAOYSA-N benzoquinolinylidene Natural products C1=CC=CC2=CC3=CC=CC=C3N=C21 DZBUGLKDJFMEHC-UHFFFAOYSA-N 0.000 description 2
- 210000002798 bone marrow cell Anatomy 0.000 description 2
- 210000004958 brain cell Anatomy 0.000 description 2
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 2
- 208000035269 cancer or benign tumor Diseases 0.000 description 2
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 2
- 230000030570 cellular localization Effects 0.000 description 2
- 238000000975 co-precipitation Methods 0.000 description 2
- 229940125773 compound 10 Drugs 0.000 description 2
- 229940125898 compound 5 Drugs 0.000 description 2
- 238000001218 confocal laser scanning microscopy Methods 0.000 description 2
- 238000010219 correlation analysis Methods 0.000 description 2
- MLIREBYILWEBDM-UHFFFAOYSA-N cyanoacetic acid Chemical compound OC(=O)CC#N MLIREBYILWEBDM-UHFFFAOYSA-N 0.000 description 2
- 125000000753 cycloalkyl group Chemical group 0.000 description 2
- 238000001739 density measurement Methods 0.000 description 2
- 230000004069 differentiation Effects 0.000 description 2
- 206010012818 diffuse large B-cell lymphoma Diseases 0.000 description 2
- LTVOKYUPTHZZQH-UHFFFAOYSA-N difluoromethane Chemical group F[C]F LTVOKYUPTHZZQH-UHFFFAOYSA-N 0.000 description 2
- 238000006073 displacement reaction Methods 0.000 description 2
- 230000036267 drug metabolism Effects 0.000 description 2
- 235000013399 edible fruits Nutrition 0.000 description 2
- 239000012636 effector Substances 0.000 description 2
- 235000013601 eggs Nutrition 0.000 description 2
- AAKJLRGGTJKAMG-UHFFFAOYSA-N erlotinib Chemical compound C=12C=C(OCCOC)C(OCCOC)=CC2=NC=NC=1NC1=CC=CC(C#C)=C1 AAKJLRGGTJKAMG-UHFFFAOYSA-N 0.000 description 2
- ZMMJGEGLRURXTF-UHFFFAOYSA-N ethidium bromide Chemical compound [Br-].C12=CC(N)=CC=C2C2=CC=C(N)C=C2[N+](CC)=C1C1=CC=CC=C1 ZMMJGEGLRURXTF-UHFFFAOYSA-N 0.000 description 2
- 229960005542 ethidium bromide Drugs 0.000 description 2
- 230000029142 excretion Effects 0.000 description 2
- 238000002875 fluorescence polarization Methods 0.000 description 2
- 210000004907 gland Anatomy 0.000 description 2
- 230000002489 hematologic effect Effects 0.000 description 2
- 125000005842 heteroatom Chemical group 0.000 description 2
- 125000002768 hydroxyalkyl group Chemical group 0.000 description 2
- 229960002411 imatinib Drugs 0.000 description 2
- 229910052738 indium Inorganic materials 0.000 description 2
- 238000001802 infusion Methods 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 238000007689 inspection Methods 0.000 description 2
- ICIWUVCWSCSTAQ-UHFFFAOYSA-M iodate Chemical compound [O-]I(=O)=O ICIWUVCWSCSTAQ-UHFFFAOYSA-M 0.000 description 2
- 150000002500 ions Chemical class 0.000 description 2
- ZLVXBBHTMQJRSX-VMGNSXQWSA-N jdtic Chemical compound C1([C@]2(C)CCN(C[C@@H]2C)C[C@H](C(C)C)NC(=O)[C@@H]2NCC3=CC(O)=CC=C3C2)=CC=CC(O)=C1 ZLVXBBHTMQJRSX-VMGNSXQWSA-N 0.000 description 2
- 230000002147 killing effect Effects 0.000 description 2
- 238000012417 linear regression Methods 0.000 description 2
- 230000007774 longterm Effects 0.000 description 2
- 208000003747 lymphoid leukemia Diseases 0.000 description 2
- 210000001161 mammalian embryo Anatomy 0.000 description 2
- 210000001259 mesencephalon Anatomy 0.000 description 2
- 230000004060 metabolic process Effects 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- 238000010172 mouse model Methods 0.000 description 2
- 238000011527 multiparameter analysis Methods 0.000 description 2
- XBGNERSKEKDZDS-UHFFFAOYSA-N n-[2-(dimethylamino)ethyl]acridine-4-carboxamide Chemical compound C1=CC=C2N=C3C(C(=O)NCCN(C)C)=CC=CC3=CC2=C1 XBGNERSKEKDZDS-UHFFFAOYSA-N 0.000 description 2
- 230000001613 neoplastic effect Effects 0.000 description 2
- 210000000441 neoplastic stem cell Anatomy 0.000 description 2
- 231100000252 nontoxic Toxicity 0.000 description 2
- 230000003000 nontoxic effect Effects 0.000 description 2
- 238000010606 normalization Methods 0.000 description 2
- 238000011275 oncology therapy Methods 0.000 description 2
- 150000004866 oxadiazoles Chemical class 0.000 description 2
- 201000008129 pancreatic ductal adenocarcinoma Diseases 0.000 description 2
- 230000036961 partial effect Effects 0.000 description 2
- 230000037361 pathway Effects 0.000 description 2
- 230000008447 perception Effects 0.000 description 2
- 239000012466 permeate Substances 0.000 description 2
- 230000000505 pernicious effect Effects 0.000 description 2
- 238000002600 positron emission tomography Methods 0.000 description 2
- 229910052700 potassium Inorganic materials 0.000 description 2
- 239000011591 potassium Substances 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 238000001556 precipitation Methods 0.000 description 2
- 230000000135 prohibitive effect Effects 0.000 description 2
- 230000001737 promoting effect Effects 0.000 description 2
- 230000004853 protein function Effects 0.000 description 2
- 239000013074 reference sample Substances 0.000 description 2
- 238000005070 sampling Methods 0.000 description 2
- 210000002966 serum Anatomy 0.000 description 2
- 239000004055 small Interfering RNA Substances 0.000 description 2
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 2
- 230000006641 stabilisation Effects 0.000 description 2
- 238000011105 stabilization Methods 0.000 description 2
- 238000010186 staining Methods 0.000 description 2
- 230000035882 stress Effects 0.000 description 2
- 238000006467 substitution reaction Methods 0.000 description 2
- 230000009885 systemic effect Effects 0.000 description 2
- 229950007866 tanespimycin Drugs 0.000 description 2
- 229940120982 tarceva Drugs 0.000 description 2
- 229960004964 temozolomide Drugs 0.000 description 2
- 238000003325 tomography Methods 0.000 description 2
- 230000002110 toxicologic effect Effects 0.000 description 2
- 230000009466 transformation Effects 0.000 description 2
- 230000014616 translation Effects 0.000 description 2
- 229960000575 trastuzumab Drugs 0.000 description 2
- 210000001635 urinary tract Anatomy 0.000 description 2
- 210000003462 vein Anatomy 0.000 description 2
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 2
- 229920002554 vinyl polymer Polymers 0.000 description 2
- UAOUIVVJBYDFKD-XKCDOFEDSA-N (1R,9R,10S,11R,12R,15S,18S,21R)-10,11,21-trihydroxy-8,8-dimethyl-14-methylidene-4-(prop-2-enylamino)-20-oxa-5-thia-3-azahexacyclo[9.7.2.112,15.01,9.02,6.012,18]henicosa-2(6),3-dien-13-one Chemical compound C([C@@H]1[C@@H](O)[C@@]23C(C1=C)=O)C[C@H]2[C@]12C(N=C(NCC=C)S4)=C4CC(C)(C)[C@H]1[C@H](O)[C@]3(O)OC2 UAOUIVVJBYDFKD-XKCDOFEDSA-N 0.000 description 1
- GLGNXYJARSMNGJ-VKTIVEEGSA-N (1s,2s,3r,4r)-3-[[5-chloro-2-[(1-ethyl-6-methoxy-2-oxo-4,5-dihydro-3h-1-benzazepin-7-yl)amino]pyrimidin-4-yl]amino]bicyclo[2.2.1]hept-5-ene-2-carboxamide Chemical compound CCN1C(=O)CCCC2=C(OC)C(NC=3N=C(C(=CN=3)Cl)N[C@H]3[C@H]([C@@]4([H])C[C@@]3(C=C4)[H])C(N)=O)=CC=C21 GLGNXYJARSMNGJ-VKTIVEEGSA-N 0.000 description 1
- SZUVGFMDDVSKSI-WIFOCOSTSA-N (1s,2s,3s,5r)-1-(carboxymethyl)-3,5-bis[(4-phenoxyphenyl)methyl-propylcarbamoyl]cyclopentane-1,2-dicarboxylic acid Chemical compound O=C([C@@H]1[C@@H]([C@](CC(O)=O)([C@H](C(=O)N(CCC)CC=2C=CC(OC=3C=CC=CC=3)=CC=2)C1)C(O)=O)C(O)=O)N(CCC)CC(C=C1)=CC=C1OC1=CC=CC=C1 SZUVGFMDDVSKSI-WIFOCOSTSA-N 0.000 description 1
- CVBWTNHDKVVFMI-LBPRGKRZSA-N (2s)-1-[4-[2-[6-amino-8-[(6-bromo-1,3-benzodioxol-5-yl)sulfanyl]purin-9-yl]ethyl]piperidin-1-yl]-2-hydroxypropan-1-one Chemical compound C1CN(C(=O)[C@@H](O)C)CCC1CCN1C2=NC=NC(N)=C2N=C1SC(C(=C1)Br)=CC2=C1OCO2 CVBWTNHDKVVFMI-LBPRGKRZSA-N 0.000 description 1
- NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 description 1
- QFLWZFQWSBQYPS-AWRAUJHKSA-N (3S)-3-[[(2S)-2-[[(2S)-2-[5-[(3aS,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoylamino]-3-methylbutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-[1-bis(4-chlorophenoxy)phosphorylbutylamino]-4-oxobutanoic acid Chemical compound CCCC(NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@@H](NC(=O)CCCCC1SC[C@@H]2NC(=O)N[C@H]12)C(C)C)P(=O)(Oc1ccc(Cl)cc1)Oc1ccc(Cl)cc1 QFLWZFQWSBQYPS-AWRAUJHKSA-N 0.000 description 1
- MWTUOSWPJOUADP-XDJHFCHBSA-N (5z)-5-(4-hydroxy-6-oxo-3-propan-2-ylcyclohexa-2,4-dien-1-ylidene)-4-(1-methylindol-5-yl)-1,2,4-triazolidin-3-one Chemical compound O=C1C=C(O)C(C(C)C)=C\C1=C\1N(C=2C=C3C=CN(C)C3=CC=2)C(=O)NN/1 MWTUOSWPJOUADP-XDJHFCHBSA-N 0.000 description 1
- DEVSOMFAQLZNKR-RJRFIUFISA-N (z)-3-[3-[3,5-bis(trifluoromethyl)phenyl]-1,2,4-triazol-1-yl]-n'-pyrazin-2-ylprop-2-enehydrazide Chemical compound FC(F)(F)C1=CC(C(F)(F)F)=CC(C2=NN(\C=C/C(=O)NNC=3N=CC=NC=3)C=N2)=C1 DEVSOMFAQLZNKR-RJRFIUFISA-N 0.000 description 1
- FTNJQNQLEGKTGD-UHFFFAOYSA-N 1,3-benzodioxole Chemical group C1=CC=C2OCOC2=C1 FTNJQNQLEGKTGD-UHFFFAOYSA-N 0.000 description 1
- KUFRQPKVAWMTJO-QSTRRNJOSA-N 17-dmag Chemical compound N1C(=O)\C(C)=C/C=C\[C@@H](OC)[C@H](OC(N)=O)\C(C)=C/[C@@H](C)[C@@H](O)[C@H](OC)C[C@@H](C)CC2=C(NCCN(C)C)C(=O)C=C1C2=O KUFRQPKVAWMTJO-QSTRRNJOSA-N 0.000 description 1
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 1
- OZDGMOYKSFPLSE-UHFFFAOYSA-N 2-Methylaziridine Chemical compound CC1CN1 OZDGMOYKSFPLSE-UHFFFAOYSA-N 0.000 description 1
- TVTJUIAKQFIXCE-HUKYDQBMSA-N 2-amino-9-[(2R,3S,4S,5R)-4-fluoro-3-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-7-prop-2-ynyl-1H-purine-6,8-dione Chemical compound NC=1NC(C=2N(C(N(C=2N=1)[C@@H]1O[C@@H]([C@H]([C@H]1O)F)CO)=O)CC#C)=O TVTJUIAKQFIXCE-HUKYDQBMSA-N 0.000 description 1
- CVOFKRWYWCSDMA-UHFFFAOYSA-N 2-chloro-n-(2,6-diethylphenyl)-n-(methoxymethyl)acetamide;2,6-dinitro-n,n-dipropyl-4-(trifluoromethyl)aniline Chemical compound CCC1=CC=CC(CC)=C1N(COC)C(=O)CCl.CCCN(CCC)C1=C([N+]([O-])=O)C=C(C(F)(F)F)C=C1[N+]([O-])=O CVOFKRWYWCSDMA-UHFFFAOYSA-N 0.000 description 1
- 238000011825 3xTg-AD mouse Methods 0.000 description 1
- QFVHZQCOUORWEI-UHFFFAOYSA-N 4-[(4-anilino-5-sulfonaphthalen-1-yl)diazenyl]-5-hydroxynaphthalene-2,7-disulfonic acid Chemical compound C=12C(O)=CC(S(O)(=O)=O)=CC2=CC(S(O)(=O)=O)=CC=1N=NC(C1=CC=CC(=C11)S(O)(=O)=O)=CC=C1NC1=CC=CC=C1 QFVHZQCOUORWEI-UHFFFAOYSA-N 0.000 description 1
- RRZVGDGTWNQAPW-UHFFFAOYSA-N 4-[5-(1-methylpyrazol-4-yl)-3-[2-(1-methylpyrazol-4-yl)ethyl]imidazol-4-yl]benzonitrile Chemical compound C1=NN(C)C=C1CCN1C(C=2C=CC(=CC=2)C#N)=C(C2=CN(C)N=C2)N=C1 RRZVGDGTWNQAPW-UHFFFAOYSA-N 0.000 description 1
- YZINASHKXHZHNQ-UHFFFAOYSA-N 5-[[4-[5-(5-chloro-2,4-dihydroxyphenyl)-1H-pyrazol-4-yl]phenyl]methylcarbamoyl]-2-(3-hydroxy-6-oxoxanthen-9-yl)benzoic acid Chemical compound OC(=O)c1cc(ccc1-c1c2ccc(O)cc2oc2cc(=O)ccc12)C(=O)NCc1ccc(cc1)-c1c[nH]nc1-c1cc(Cl)c(O)cc1O YZINASHKXHZHNQ-UHFFFAOYSA-N 0.000 description 1
- UYODNJZBUUEXPC-UHFFFAOYSA-N 9-[2-(2,2-dimethylpropylamino)ethyl]-8-[(6-iodo-1,3-benzodioxol-5-yl)sulfanyl]purin-6-amine Chemical compound N1=CN=C2N(CCNCC(C)(C)C)C(SC=3C(=CC=4OCOC=4C=3)I)=NC2=C1N UYODNJZBUUEXPC-UHFFFAOYSA-N 0.000 description 1
- 208000002874 Acne Vulgaris Diseases 0.000 description 1
- 102100022900 Actin, cytoplasmic 1 Human genes 0.000 description 1
- 108010085238 Actins Proteins 0.000 description 1
- 229920000936 Agarose Polymers 0.000 description 1
- 229940126638 Akt inhibitor Drugs 0.000 description 1
- 208000037259 Amyloid Plaque Diseases 0.000 description 1
- 102000000412 Annexin Human genes 0.000 description 1
- 108050008874 Annexin Proteins 0.000 description 1
- 101100261173 Arabidopsis thaliana TPS7 gene Proteins 0.000 description 1
- 241000208340 Araliaceae Species 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- 208000003950 B-cell lymphoma Diseases 0.000 description 1
- QULDDKSCVCJTPV-UHFFFAOYSA-N BIIB021 Chemical compound COC1=C(C)C=NC(CN2C3=NC(N)=NC(Cl)=C3N=C2)=C1C QULDDKSCVCJTPV-UHFFFAOYSA-N 0.000 description 1
- 229940118364 Bcr-Abl inhibitor Drugs 0.000 description 1
- 206010005003 Bladder cancer Diseases 0.000 description 1
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 description 1
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 description 1
- 101150010856 CRT gene Proteins 0.000 description 1
- 101100484538 Caenorhabditis elegans vav-1 gene Proteins 0.000 description 1
- 206010057248 Cell death Diseases 0.000 description 1
- 241001232809 Chorista Species 0.000 description 1
- 108010058546 Cyclin D1 Proteins 0.000 description 1
- ZBNZXTGUTAYRHI-UHFFFAOYSA-N Dasatinib Chemical compound C=1C(N2CCN(CCO)CC2)=NC(C)=NC=1NC(S1)=NC=C1C(=O)NC1=C(C)C=CC=C1Cl ZBNZXTGUTAYRHI-UHFFFAOYSA-N 0.000 description 1
- 208000030453 Drug-Related Side Effects and Adverse reaction Diseases 0.000 description 1
- 102100039369 Epidermal growth factor receptor substrate 15 Human genes 0.000 description 1
- 238000000729 Fisher's exact test Methods 0.000 description 1
- 108091006027 G proteins Proteins 0.000 description 1
- 102100024165 G1/S-specific cyclin-D1 Human genes 0.000 description 1
- 102100024185 G1/S-specific cyclin-D2 Human genes 0.000 description 1
- 102000030782 GTP binding Human genes 0.000 description 1
- 108091000058 GTP-Binding Proteins 0.000 description 1
- 208000022072 Gallbladder Neoplasms Diseases 0.000 description 1
- 102100031181 Glyceraldehyde-3-phosphate dehydrogenase Human genes 0.000 description 1
- 206010018498 Goitre Diseases 0.000 description 1
- 102100033067 Growth factor receptor-bound protein 2 Human genes 0.000 description 1
- 108010004889 Heat-Shock Proteins Proteins 0.000 description 1
- 102000002812 Heat-Shock Proteins Human genes 0.000 description 1
- 101000812517 Homo sapiens Epidermal growth factor receptor substrate 15 Proteins 0.000 description 1
- 101000980741 Homo sapiens G1/S-specific cyclin-D2 Proteins 0.000 description 1
- 101000871017 Homo sapiens Growth factor receptor-bound protein 2 Proteins 0.000 description 1
- 101000757232 Homo sapiens Protein arginine N-methyltransferase 2 Proteins 0.000 description 1
- 101000932478 Homo sapiens Receptor-type tyrosine-protein kinase FLT3 Proteins 0.000 description 1
- 108010091358 Hypoxanthine Phosphoribosyltransferase Proteins 0.000 description 1
- 102100029098 Hypoxanthine-guanine phosphoribosyltransferase Human genes 0.000 description 1
- 208000005016 Intestinal Neoplasms Diseases 0.000 description 1
- 229940122245 Janus kinase inhibitor Drugs 0.000 description 1
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 1
- 239000002067 L01XE06 - Dasatinib Substances 0.000 description 1
- 208000007433 Lymphatic Metastasis Diseases 0.000 description 1
- 208000031422 Lymphocytic Chronic B-Cell Leukemia Diseases 0.000 description 1
- 230000005723 MEK inhibition Effects 0.000 description 1
- 229940124647 MEK inhibitor Drugs 0.000 description 1
- 206010027336 Menstruation delayed Diseases 0.000 description 1
- 108090000744 Mitogen-Activated Protein Kinase Kinases Proteins 0.000 description 1
- 102000004232 Mitogen-Activated Protein Kinase Kinases Human genes 0.000 description 1
- 108010006519 Molecular Chaperones Proteins 0.000 description 1
- 229910020700 Na3VO4 Inorganic materials 0.000 description 1
- QJGQUHMNIGDVPM-BJUDXGSMSA-N Nitrogen-13 Chemical compound [13N] QJGQUHMNIGDVPM-BJUDXGSMSA-N 0.000 description 1
- 101100522110 Oryza sativa subsp. japonica PHT1-10 gene Proteins 0.000 description 1
- 101100522114 Oryza sativa subsp. japonica PHT1-12 gene Proteins 0.000 description 1
- 108010011536 PTEN Phosphohydrolase Proteins 0.000 description 1
- 102000014160 PTEN Phosphohydrolase Human genes 0.000 description 1
- 235000005035 Panax pseudoginseng ssp. pseudoginseng Nutrition 0.000 description 1
- 235000003140 Panax quinquefolius Nutrition 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- 101100522109 Pinus taeda PT10 gene Proteins 0.000 description 1
- 101100410148 Pinus taeda PT30 gene Proteins 0.000 description 1
- 108010003506 Protein Kinase D2 Proteins 0.000 description 1
- 102100034607 Protein arginine N-methyltransferase 5 Human genes 0.000 description 1
- 101710084427 Protein arginine N-methyltransferase 5 Proteins 0.000 description 1
- 108010045292 Proto-Oncogene Proteins c-abl Proteins 0.000 description 1
- 102000005663 Proto-Oncogene Proteins c-abl Human genes 0.000 description 1
- 108010029869 Proto-Oncogene Proteins c-raf Proteins 0.000 description 1
- 102000001788 Proto-Oncogene Proteins c-raf Human genes 0.000 description 1
- 238000011529 RT qPCR Methods 0.000 description 1
- 101710100969 Receptor tyrosine-protein kinase erbB-3 Proteins 0.000 description 1
- 102100029986 Receptor tyrosine-protein kinase erbB-3 Human genes 0.000 description 1
- 102100020718 Receptor-type tyrosine-protein kinase FLT3 Human genes 0.000 description 1
- YJDYDFNKCBANTM-QCWCSKBGSA-N SDZ PSC 833 Chemical compound C\C=C\C[C@@H](C)C(=O)[C@@H]1N(C)C(=O)[C@H](C(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)N(C)C(=O)CN(C)C(=O)[C@H](C(C)C)NC1=O YJDYDFNKCBANTM-QCWCSKBGSA-N 0.000 description 1
- 235000013290 Sagittaria latifolia Nutrition 0.000 description 1
- 101100440247 Schizosaccharomyces pombe (strain 972 / ATCC 24843) cnd2 gene Proteins 0.000 description 1
- 102100037312 Serine/threonine-protein kinase D2 Human genes 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 108020004459 Small interfering RNA Proteins 0.000 description 1
- 101150043341 Socs3 gene Proteins 0.000 description 1
- 206010041660 Splenomegaly Diseases 0.000 description 1
- 102000058015 Suppressor of Cytokine Signaling 3 Human genes 0.000 description 1
- 108700027337 Suppressor of Cytokine Signaling 3 Proteins 0.000 description 1
- 229940100514 Syk tyrosine kinase inhibitor Drugs 0.000 description 1
- 206010070863 Toxicity to various agents Diseases 0.000 description 1
- 102100033019 Tyrosine-protein phosphatase non-receptor type 11 Human genes 0.000 description 1
- 101710116241 Tyrosine-protein phosphatase non-receptor type 11 Proteins 0.000 description 1
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 description 1
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 description 1
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 description 1
- GLQOALGKMKUSBF-UHFFFAOYSA-N [amino(diphenyl)silyl]benzene Chemical compound C=1C=CC=CC=1[Si](C=1C=CC=CC=1)(N)C1=CC=CC=C1 GLQOALGKMKUSBF-UHFFFAOYSA-N 0.000 description 1
- 230000003187 abdominal effect Effects 0.000 description 1
- 239000000370 acceptor Substances 0.000 description 1
- 206010000496 acne Diseases 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 102000035181 adaptor proteins Human genes 0.000 description 1
- 108091005764 adaptor proteins Proteins 0.000 description 1
- 230000002730 additional effect Effects 0.000 description 1
- 230000001464 adherent effect Effects 0.000 description 1
- 125000003342 alkenyl group Chemical group 0.000 description 1
- 125000002355 alkine group Chemical group 0.000 description 1
- 125000004948 alkyl aryl alkyl group Chemical group 0.000 description 1
- 230000029936 alkylation Effects 0.000 description 1
- 238000005804 alkylation reaction Methods 0.000 description 1
- 229950007861 alvespimycin Drugs 0.000 description 1
- 125000003368 amide group Chemical group 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 230000003321 amplification Effects 0.000 description 1
- 210000003484 anatomy Anatomy 0.000 description 1
- 230000000118 anti-neoplastic effect Effects 0.000 description 1
- 230000002579 anti-swelling effect Effects 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 229940034982 antineoplastic agent Drugs 0.000 description 1
- 230000001640 apoptogenic effect Effects 0.000 description 1
- 210000001367 artery Anatomy 0.000 description 1
- 125000003710 aryl alkyl group Chemical group 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 108700000711 bcl-X Proteins 0.000 description 1
- 102000055104 bcl-X Human genes 0.000 description 1
- 125000005605 benzo group Chemical group 0.000 description 1
- 239000013060 biological fluid Substances 0.000 description 1
- 230000008827 biological function Effects 0.000 description 1
- 230000008236 biological pathway Effects 0.000 description 1
- 239000012472 biological sample Substances 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 230000036765 blood level Effects 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 239000007767 bonding agent Substances 0.000 description 1
- 238000009583 bone marrow aspiration Methods 0.000 description 1
- 229910000024 caesium carbonate Inorganic materials 0.000 description 1
- 239000012830 cancer therapeutic Substances 0.000 description 1
- 150000001721 carbon Chemical class 0.000 description 1
- OKTJSMMVPCPJKN-BJUDXGSMSA-N carbon-11 Chemical compound [11C] OKTJSMMVPCPJKN-BJUDXGSMSA-N 0.000 description 1
- 231100000357 carcinogen Toxicity 0.000 description 1
- 231100000504 carcinogenesis Toxicity 0.000 description 1
- 239000003183 carcinogenic agent Substances 0.000 description 1
- 230000000747 cardiac effect Effects 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 239000002458 cell surface marker Substances 0.000 description 1
- VDQQXEISLMTGAB-UHFFFAOYSA-N chloramine T Chemical compound [Na+].CC1=CC=C(S(=O)(=O)[N-]Cl)C=C1 VDQQXEISLMTGAB-UHFFFAOYSA-N 0.000 description 1
- DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 description 1
- 229960004316 cisplatin Drugs 0.000 description 1
- 238000004140 cleaning Methods 0.000 description 1
- 230000003081 coactivator Effects 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 235000015246 common arrowhead Nutrition 0.000 description 1
- 229940126543 compound 14 Drugs 0.000 description 1
- 229940125758 compound 15 Drugs 0.000 description 1
- 229940125851 compound 27 Drugs 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 238000012790 confirmation Methods 0.000 description 1
- 230000001276 controlling effect Effects 0.000 description 1
- 239000013256 coordination polymer Substances 0.000 description 1
- 230000002596 correlated effect Effects 0.000 description 1
- 230000000875 corresponding effect Effects 0.000 description 1
- 238000005336 cracking Methods 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 230000009089 cytolysis Effects 0.000 description 1
- 210000000172 cytosol Anatomy 0.000 description 1
- 230000001086 cytosolic effect Effects 0.000 description 1
- 229940127089 cytotoxic agent Drugs 0.000 description 1
- 239000002254 cytotoxic agent Substances 0.000 description 1
- 231100000599 cytotoxic agent Toxicity 0.000 description 1
- 229960002448 dasatinib Drugs 0.000 description 1
- 238000007405 data analysis Methods 0.000 description 1
- 238000013480 data collection Methods 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000005695 dehalogenation reaction Methods 0.000 description 1
- 238000000151 deposition Methods 0.000 description 1
- 230000000994 depressogenic effect Effects 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 238000002059 diagnostic imaging Methods 0.000 description 1
- 238000006471 dimerization reaction Methods 0.000 description 1
- 238000001647 drug administration Methods 0.000 description 1
- 238000009509 drug development Methods 0.000 description 1
- 239000002359 drug metabolite Substances 0.000 description 1
- 238000000295 emission spectrum Methods 0.000 description 1
- 102000052116 epidermal growth factor receptor activity proteins Human genes 0.000 description 1
- 108700015053 epidermal growth factor receptor activity proteins Proteins 0.000 description 1
- 230000007717 exclusion Effects 0.000 description 1
- 208000021045 exocrine pancreatic carcinoma Diseases 0.000 description 1
- 238000013401 experimental design Methods 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 239000004744 fabric Substances 0.000 description 1
- 238000002189 fluorescence spectrum Methods 0.000 description 1
- YCKRFDGAMUMZLT-BJUDXGSMSA-N fluorine-18 atom Chemical compound [18F] YCKRFDGAMUMZLT-BJUDXGSMSA-N 0.000 description 1
- 229950004161 ganetespib Drugs 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 235000008434 ginseng Nutrition 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 229940080856 gleevec Drugs 0.000 description 1
- 108020004445 glyceraldehyde-3-phosphate dehydrogenase Proteins 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 210000002768 hair cell Anatomy 0.000 description 1
- 208000014829 head and neck neoplasm Diseases 0.000 description 1
- 208000018706 hematopoietic system disease Diseases 0.000 description 1
- 230000002440 hepatic effect Effects 0.000 description 1
- 230000010224 hepatic metabolism Effects 0.000 description 1
- 125000001072 heteroaryl group Chemical group 0.000 description 1
- 125000004446 heteroarylalkyl group Chemical group 0.000 description 1
- 210000001320 hippocampus Anatomy 0.000 description 1
- 239000000710 homodimer Substances 0.000 description 1
- 102000046485 human PRMT2 Human genes 0.000 description 1
- 210000005260 human cell Anatomy 0.000 description 1
- 239000010903 husk Substances 0.000 description 1
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 1
- UPJHGMQWKSHELY-UHFFFAOYSA-N hydrazine;isoindole-1,3-dione Chemical compound NN.C1=CC=C2C(=O)NC(=O)C2=C1 UPJHGMQWKSHELY-UHFFFAOYSA-N 0.000 description 1
- 150000002431 hydrogen Chemical class 0.000 description 1
- 230000001969 hypertrophic effect Effects 0.000 description 1
- KTUFNOKKBVMGRW-UHFFFAOYSA-N imatinib Chemical compound C1CN(C)CCN1CC1=CC=C(C(=O)NC=2C=C(NC=3N=C(C=CN=3)C=3C=NC=CC=3)C(C)=CC=2)C=C1 KTUFNOKKBVMGRW-UHFFFAOYSA-N 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 238000002513 implantation Methods 0.000 description 1
- 230000001976 improved effect Effects 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 230000008595 infiltration Effects 0.000 description 1
- 238000001764 infiltration Methods 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 238000013152 interventional procedure Methods 0.000 description 1
- 201000002313 intestinal cancer Diseases 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 239000007928 intraperitoneal injection Substances 0.000 description 1
- 230000009545 invasion Effects 0.000 description 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
- XMBWDFGMSWQBCA-RNFDNDRNSA-M iodine-131(1-) Chemical compound [131I-] XMBWDFGMSWQBCA-RNFDNDRNSA-M 0.000 description 1
- 239000010410 layer Substances 0.000 description 1
- 238000002514 liquid chromatography mass spectrum Methods 0.000 description 1
- 210000005229 liver cell Anatomy 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 210000002540 macrophage Anatomy 0.000 description 1
- 230000005741 malignant process Effects 0.000 description 1
- 208000026037 malignant tumor of neck Diseases 0.000 description 1
- 238000007726 management method Methods 0.000 description 1
- 201000007924 marginal zone B-cell lymphoma Diseases 0.000 description 1
- 208000021937 marginal zone lymphoma Diseases 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 108020004999 messenger RNA Proteins 0.000 description 1
- 208000037819 metastatic cancer Diseases 0.000 description 1
- 208000011575 metastatic malignant neoplasm Diseases 0.000 description 1
- 239000002829 mitogen activated protein kinase inhibitor Substances 0.000 description 1
- 229940125374 mitogen-activated extracellular signal-regulated kinase inhibitor Drugs 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 210000000865 mononuclear phagocyte system Anatomy 0.000 description 1
- 230000000877 morphologic effect Effects 0.000 description 1
- 208000025113 myeloid leukemia Diseases 0.000 description 1
- 230000002071 myeloproliferative effect Effects 0.000 description 1
- YOHYSYJDKVYCJI-UHFFFAOYSA-N n-[3-[[6-[3-(trifluoromethyl)anilino]pyrimidin-4-yl]amino]phenyl]cyclopropanecarboxamide Chemical compound FC(F)(F)C1=CC=CC(NC=2N=CN=C(NC=3C=C(NC(=O)C4CC4)C=CC=3)C=2)=C1 YOHYSYJDKVYCJI-UHFFFAOYSA-N 0.000 description 1
- 210000004897 n-terminal region Anatomy 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 239000013642 negative control Substances 0.000 description 1
- 230000010309 neoplastic transformation Effects 0.000 description 1
- 230000004770 neurodegeneration Effects 0.000 description 1
- 208000015122 neurodegenerative disease Diseases 0.000 description 1
- LQNUZADURLCDLV-UHFFFAOYSA-N nitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC=C1 LQNUZADURLCDLV-UHFFFAOYSA-N 0.000 description 1
- 238000012633 nuclear imaging Methods 0.000 description 1
- 238000003199 nucleic acid amplification method Methods 0.000 description 1
- 231100000590 oncogenic Toxicity 0.000 description 1
- 230000002246 oncogenic effect Effects 0.000 description 1
- WCPAKWJPBJAGKN-UHFFFAOYSA-N oxadiazole Chemical compound C1=CON=N1 WCPAKWJPBJAGKN-UHFFFAOYSA-N 0.000 description 1
- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 1
- 201000002094 pancreatic adenocarcinoma Diseases 0.000 description 1
- 238000002262 pancreatoduodenectomy Methods 0.000 description 1
- 230000007918 pathogenicity Effects 0.000 description 1
- 239000011049 pearl Substances 0.000 description 1
- 230000000149 penetrating effect Effects 0.000 description 1
- 239000002304 perfume Substances 0.000 description 1
- 210000003819 peripheral blood mononuclear cell Anatomy 0.000 description 1
- 230000002688 persistence Effects 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- DCWXELXMIBXGTH-UHFFFAOYSA-N phosphotyrosine Chemical compound OC(=O)C(N)CC1=CC=C(OP(O)(O)=O)C=C1 DCWXELXMIBXGTH-UHFFFAOYSA-N 0.000 description 1
- 230000037081 physical activity Effects 0.000 description 1
- 230000035479 physiological effects, processes and functions Effects 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Substances [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 1
- 210000004224 pleura Anatomy 0.000 description 1
- 238000002264 polyacrylamide gel electrophoresis Methods 0.000 description 1
- 229920000573 polyethylene Polymers 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 230000002980 postoperative effect Effects 0.000 description 1
- 235000007715 potassium iodide Nutrition 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 238000003825 pressing Methods 0.000 description 1
- 238000002203 pretreatment Methods 0.000 description 1
- 208000037821 progressive disease Diseases 0.000 description 1
- 229940121649 protein inhibitor Drugs 0.000 description 1
- 239000012268 protein inhibitor Substances 0.000 description 1
- 238000001243 protein synthesis Methods 0.000 description 1
- 150000003217 pyrazoles Chemical class 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
- 238000011002 quantification Methods 0.000 description 1
- 238000006862 quantum yield reaction Methods 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 230000002285 radioactive effect Effects 0.000 description 1
- 238000000611 regression analysis Methods 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 238000009256 replacement therapy Methods 0.000 description 1
- 239000004576 sand Substances 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 239000012047 saturated solution Substances 0.000 description 1
- 238000009738 saturating Methods 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 150000003335 secondary amines Chemical class 0.000 description 1
- 210000000717 sertoli cell Anatomy 0.000 description 1
- 238000011125 single therapy Methods 0.000 description 1
- 210000002027 skeletal muscle Anatomy 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 230000003595 spectral effect Effects 0.000 description 1
- 235000013599 spices Nutrition 0.000 description 1
- 238000011272 standard treatment Methods 0.000 description 1
- 238000009955 starching Methods 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 230000031068 symbiosis, encompassing mutualism through parasitism Effects 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 239000012622 synthetic inhibitor Substances 0.000 description 1
- 229940126703 systemic medication Drugs 0.000 description 1
- 238000004885 tandem mass spectrometry Methods 0.000 description 1
- MPLHNVLQVRSVEE-UHFFFAOYSA-N texas red Chemical compound [O-]S(=O)(=O)C1=CC(S(Cl)(=O)=O)=CC=C1C(C1=CC=2CCCN3CCCC(C=23)=C1O1)=C2C1=C(CCC1)C3=[N+]1CCCC3=C2 MPLHNVLQVRSVEE-UHFFFAOYSA-N 0.000 description 1
- 230000004797 therapeutic response Effects 0.000 description 1
- DPJRMOMPQZCRJU-UHFFFAOYSA-M thiamine hydrochloride Chemical compound Cl.[Cl-].CC1=C(CCO)SC=[N+]1CC1=CN=C(C)N=C1N DPJRMOMPQZCRJU-UHFFFAOYSA-M 0.000 description 1
- 229960001479 tosylchloramide sodium Drugs 0.000 description 1
- 238000013519 translation Methods 0.000 description 1
- 238000002054 transplantation Methods 0.000 description 1
- 238000012384 transportation and delivery Methods 0.000 description 1
- DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 1
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 1
- CCRMAATUKBYMPA-UHFFFAOYSA-N trimethyltin Chemical compound C[Sn](C)C.C[Sn](C)C CCRMAATUKBYMPA-UHFFFAOYSA-N 0.000 description 1
- IHIXIJGXTJIKRB-UHFFFAOYSA-N trisodium vanadate Chemical compound [Na+].[Na+].[Na+].[O-][V]([O-])([O-])=O IHIXIJGXTJIKRB-UHFFFAOYSA-N 0.000 description 1
- 201000008827 tuberculosis Diseases 0.000 description 1
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
- 238000002525 ultrasonication Methods 0.000 description 1
- 238000011144 upstream manufacturing Methods 0.000 description 1
- 210000000626 ureter Anatomy 0.000 description 1
- 210000003932 urinary bladder Anatomy 0.000 description 1
- 201000005112 urinary bladder cancer Diseases 0.000 description 1
- 210000002700 urine Anatomy 0.000 description 1
- 229950010938 valspodar Drugs 0.000 description 1
- 108010082372 valspodar Proteins 0.000 description 1
- LSGOVYNHVSXFFJ-UHFFFAOYSA-N vanadate(3-) Chemical compound [O-][V]([O-])([O-])=O LSGOVYNHVSXFFJ-UHFFFAOYSA-N 0.000 description 1
- QCWXUUIWCKQGHC-YPZZEJLDSA-N zirconium-89 Chemical compound [89Zr] QCWXUUIWCKQGHC-YPZZEJLDSA-N 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K51/00—Preparations containing radioactive substances for use in therapy or testing in vivo
- A61K51/02—Preparations containing radioactive substances for use in therapy or testing in vivo characterised by the carrier, i.e. characterised by the agent or material covalently linked or complexing the radioactive nucleus
- A61K51/04—Organic compounds
- A61K51/041—Heterocyclic compounds
- A61K51/044—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine, rifamycins
- A61K51/0459—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine, rifamycins having six-membered rings with two nitrogen atoms as the only ring hetero atoms, e.g. piperazine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
- A61K31/52—Purines, e.g. adenine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/5005—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells
- G01N33/5008—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics
- G01N33/5011—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics for testing antineoplastic activity
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/5005—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells
- G01N33/5008—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics
- G01N33/5014—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics for testing toxicity
- G01N33/5017—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics for testing toxicity for testing neoplastic activity
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/574—Immunoassay; Biospecific binding assay; Materials therefor for cancer
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/574—Immunoassay; Biospecific binding assay; Materials therefor for cancer
- G01N33/57407—Specifically defined cancers
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/574—Immunoassay; Biospecific binding assay; Materials therefor for cancer
- G01N33/57407—Specifically defined cancers
- G01N33/57426—Specifically defined cancers leukemia
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
- G01N33/6893—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids related to diseases not provided for elsewhere
- G01N33/6896—Neurological disorders, e.g. Alzheimer's disease
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2500/00—Screening for compounds of potential therapeutic value
- G01N2500/04—Screening involving studying the effect of compounds C directly on molecule A (e.g. C are potential ligands for a receptor A, or potential substrates for an enzyme A)
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2800/00—Detection or diagnosis of diseases
- G01N2800/52—Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/5005—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells
- G01N33/5008—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics
- G01N33/5044—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics involving specific cell types
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Immunology (AREA)
- Chemical & Material Sciences (AREA)
- Biomedical Technology (AREA)
- Hematology (AREA)
- Urology & Nephrology (AREA)
- Molecular Biology (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Physics & Mathematics (AREA)
- Cell Biology (AREA)
- Pathology (AREA)
- Microbiology (AREA)
- Analytical Chemistry (AREA)
- Biochemistry (AREA)
- Food Science & Technology (AREA)
- Biotechnology (AREA)
- General Physics & Mathematics (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Oncology (AREA)
- Hospice & Palliative Care (AREA)
- Epidemiology (AREA)
- Toxicology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Tropical Medicine & Parasitology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Optics & Photonics (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Investigating Or Analysing Biological Materials (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201161506010P | 2011-07-08 | 2011-07-08 | |
| US61/506,010 | 2011-07-08 | ||
| PCT/US2012/045864 WO2013009657A1 (en) | 2011-07-08 | 2012-07-06 | Uses of labeled hsp90 inhibitors |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN104081206A CN104081206A (zh) | 2014-10-01 |
| CN104081206B true CN104081206B (zh) | 2017-06-09 |
Family
ID=47506428
Family Applications (3)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201280040606.7A Expired - Fee Related CN104081206B (zh) | 2011-07-08 | 2012-07-06 | 标记的hsp90抑制剂的用途 |
| CN201810715481.2A Active CN109374889B (zh) | 2011-07-08 | 2012-07-06 | 标记的hsp90抑制剂的用途 |
| CN201280040632.XA Expired - Fee Related CN104081203B (zh) | 2011-07-08 | 2012-07-06 | 标记的hsp90抑制剂的用途 |
Family Applications After (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201810715481.2A Active CN109374889B (zh) | 2011-07-08 | 2012-07-06 | 标记的hsp90抑制剂的用途 |
| CN201280040632.XA Expired - Fee Related CN104081203B (zh) | 2011-07-08 | 2012-07-06 | 标记的hsp90抑制剂的用途 |
Country Status (14)
| Country | Link |
|---|---|
| US (4) | US9555137B2 (es) |
| EP (3) | EP3709022A1 (es) |
| JP (4) | JP6054389B2 (es) |
| KR (2) | KR102138218B1 (es) |
| CN (3) | CN104081206B (es) |
| AU (3) | AU2012282903A1 (es) |
| BR (1) | BR112014000445A2 (es) |
| CA (2) | CA2841069C (es) |
| DK (1) | DK2729806T3 (es) |
| EA (1) | EA201490230A1 (es) |
| ES (2) | ES2624982T3 (es) |
| HK (1) | HK1243175A1 (es) |
| MX (2) | MX347607B (es) |
| WO (2) | WO2013009657A1 (es) |
Families Citing this family (22)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US9403828B2 (en) | 2005-02-01 | 2016-08-02 | Sloan-Kettering Institute For Cancer Research | Small-molecule Hsp90 inhibitors |
| US7834181B2 (en) | 2005-02-01 | 2010-11-16 | Slaon-Kettering Institute For Cancer Research | Small-molecule Hsp90 inhibitors |
| JP6054389B2 (ja) | 2011-07-08 | 2016-12-27 | スローン − ケタリング・インスティテュート・フォー・キャンサー・リサーチ | 標識されたｈｓｐ９０阻害剤の使用 |
| JP6678455B2 (ja) | 2012-12-21 | 2020-04-08 | エピザイム，インコーポレイティド | Ｐｒｍｔ５阻害剤およびその使用 |
| CA2905509A1 (en) | 2013-03-15 | 2014-09-18 | Memorial Sloan-Kettering Cancer Center | Hsp90-targeted cardiac imaging and therapy |
| CN103279964B (zh) * | 2013-04-23 | 2015-10-28 | 浙江大学 | 一种基于prca的pet图像动态重建方法及系统 |
| AU2014306417C1 (en) | 2013-08-16 | 2019-07-25 | Memorial Sloan-Kettering Cancer Center | Selective Grp94 inhibitors and uses thereof |
| WO2015038649A1 (en) * | 2013-09-10 | 2015-03-19 | Synta Pharmaceuticals Corp. | Targeted therapeutics |
| JP6497767B2 (ja) * | 2013-12-16 | 2019-04-10 | 日本化薬株式会社 | 癌治療におけるｈｓｐ９０阻害剤の抗腫瘍効果を予測する方法 |
| RU2016128528A (ru) | 2013-12-23 | 2018-01-30 | Мемориал Слоун-Кеттеринг Кэнсэ Сентр | Способы и реактивы для введения радиоактивной метки |
| EP2942629A1 (en) * | 2014-05-08 | 2015-11-11 | Universität Würzburg | Predictive markers for successful cancer immunotherapy |
| CN107110869B (zh) | 2014-09-17 | 2021-08-10 | 纪念斯隆-凯特琳癌症中心 | Hsp90-靶向炎症和感染成像及治疗 |
| KR20180058824A (ko) | 2015-10-05 | 2018-06-01 | 메모리얼 슬로안-케터링 캔서 센터 | 암 치료를 위한 합리적 병용 요법 |
| RS60209B1 (sr) | 2017-03-20 | 2020-06-30 | Forma Therapeutics Inc | Kompozicije pirolopirola kao aktivatori piruvat kinaze (pkr) |
| CN111386351A (zh) * | 2017-09-22 | 2020-07-07 | 华盛顿大学 | 细胞分子的原位组合标记 |
| US20220031671A1 (en) | 2018-09-19 | 2022-02-03 | Forma Therapeutics, Inc. | Treating sickle cell disease with a pyruvate kinase r activating compound |
| WO2020061255A1 (en) | 2018-09-19 | 2020-03-26 | Forma Therapeutics, Inc. | Activating pyruvate kinase r |
| US11493519B2 (en) | 2019-02-08 | 2022-11-08 | Dewpoint Therapeutics, Inc. | Methods of characterizing condensate-associated characteristics of compounds and uses thereof |
| CN114173879A (zh) * | 2019-05-15 | 2022-03-11 | 怀特黑德生物医学研究所 | 表征和利用药剂-凝聚物相互作用的方法 |
| CN114729941A (zh) | 2019-09-18 | 2022-07-08 | 露点治疗公司 | 筛选凝聚物相关特异性的方法及其用途 |
| WO2022072694A1 (en) * | 2020-10-02 | 2022-04-07 | The Trustees Of Dartmouth College | Method and agent for treating/preventing neurodegenerative disease and associated neuroinflammation and for evaluating putative prophylactics/therapeutics for treating/preventing neurodegenerative disease and neuroinflammation |
| CN113025715A (zh) * | 2021-03-23 | 2021-06-25 | 中山大学附属第一医院 | Hop在预测胃癌预后中的应用 |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1860132A (zh) * | 2003-03-12 | 2006-11-08 | 塔夫兹大学 | 细胞外Hsp90的抑制剂 |
| WO2010020618A1 (en) * | 2008-08-18 | 2010-02-25 | MAX-PLANCK-Gesellschaft zur Förderung der Wissenschaften e.V. | Susceptibility to hsp90-inhibitors |
| CN101854955A (zh) * | 2007-09-10 | 2010-10-06 | 马萨诸塞大学 | 靶向线粒体的抗肿瘤剂 |
Family Cites Families (31)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7156111B2 (en) * | 2001-07-16 | 2007-01-02 | Akrion Technologies, Inc | Megasonic cleaning using supersaturated cleaning solution |
| US20050074457A1 (en) * | 2001-12-12 | 2005-04-07 | Adeela Kamal | Assays and implements for determining and modulating hsp90 binding activity |
| US20040121971A1 (en) * | 2002-12-20 | 2004-06-24 | Gang Chen | Therapeutic use of tumor necrosis factor-alpha mutein |
| US7959915B2 (en) * | 2003-03-12 | 2011-06-14 | Tufts University | Inhibitors of extracellular Hsp90 |
| WO2005012482A2 (en) * | 2003-06-30 | 2005-02-10 | Sloan-Kettering Institute For Cancer Research | Assay for identification of bioactive compounds that interact with heat shock protein 90 |
| EP1675861B1 (en) | 2003-08-29 | 2015-12-23 | Vernalis (R&D) Ltd. | Pyrimidothiophene compounds |
| GB0323810D0 (en) * | 2003-10-10 | 2003-11-12 | Cancer Rec Tech Ltd | Pyridothiophene compounds |
| CN1922304A (zh) * | 2003-10-31 | 2007-02-28 | 维特克公司 | 用于检测循环肿瘤和内皮细胞的血液测试样机和方法 |
| US7834181B2 (en) | 2005-02-01 | 2010-11-16 | Slaon-Kettering Institute For Cancer Research | Small-molecule Hsp90 inhibitors |
| US9403828B2 (en) | 2005-02-01 | 2016-08-02 | Sloan-Kettering Institute For Cancer Research | Small-molecule Hsp90 inhibitors |
| EP1946115A4 (en) * | 2005-10-21 | 2009-12-02 | Bayer Healthcare Llc | METHOD FOR PREDICTING AND FORECASTING CANCER AND MONITORING CANCER THERAPY |
| DE102006023336A1 (de) | 2006-05-18 | 2007-11-22 | Merck Patent Gmbh | 1,5-Diphenyl-pyrazole II |
| EP2034996A2 (en) | 2006-05-25 | 2009-03-18 | Synta Pharmaceuticals Corporation | Triazole compounds that modulate hsp90 activity |
| AU2007269144B2 (en) * | 2006-06-30 | 2013-05-16 | Sloan-Kettering Institute For Cancer Research | Treatment of neurodegenerative diseases through inhibition of HSP90 |
| US8580519B2 (en) * | 2006-11-27 | 2013-11-12 | University Of Maryland, Baltimore | Use of plasma HSP90 related to malignancy |
| US20090092974A1 (en) * | 2006-12-08 | 2009-04-09 | Asuragen, Inc. | Micrornas differentially expressed in leukemia and uses thereof |
| WO2008128093A1 (en) * | 2007-04-13 | 2008-10-23 | Pharmacyclics, Inc. | Calcium flux as a pharmacoefficacy biomarker for inhibitors of histone deacetylase |
| AU2008310664A1 (en) * | 2007-10-12 | 2009-04-16 | Transmolecular, Inc. | Systemic administration of chlorotoxin agents for the diagnosis and treatment of tumors |
| AU2008333786A1 (en) * | 2007-12-07 | 2009-06-11 | Bipar Sciences, Inc. | Treatment of cancer with combinations of topoisomerase inhibitors and PARP inhibitors |
| CN102144163A (zh) | 2008-04-10 | 2011-08-03 | 麻省理工学院 | 关于鉴定和使用靶向癌症干细胞的试剂的方法 |
| MX353747B (es) * | 2009-08-17 | 2018-01-26 | Memorial Sloan Kettering Cancer Center Star | Compuesto de union a proteina de choque termico, composiciones, y metodos para producir y usar los mismos. |
| ES2733131T3 (es) * | 2009-10-07 | 2019-11-27 | Sloan Kettering Inst Cancer Res | Derivados de purina útiles como inhibidores de hsp90 |
| CA2779843A1 (en) | 2009-11-13 | 2011-05-19 | Infinity Pharmaceuticals, Inc. | Compositions, kits, and methods for identification, assessment, prevention, and therapy of cancer |
| US8710035B2 (en) | 2010-03-24 | 2014-04-29 | The University Of Chicago | Methods and compositions related to glucocorticoid receptor antagonists and breast cancer |
| EA024647B1 (ru) | 2011-04-05 | 2016-10-31 | Слоун-Кеттеринг Инститьют Фо Кэнсэ Рисерч | ИНГИБИТОРЫ Hsp90 |
| CN103582642B (zh) | 2011-04-05 | 2021-05-11 | 索隆-基特林癌症研究协会 | Hsp90抑制剂 |
| BR112013027448A2 (pt) | 2011-04-28 | 2020-09-01 | Sloan-Kettering Institute For Cancer Research | terapia de combinação com hsp90 |
| JP6054389B2 (ja) | 2011-07-08 | 2016-12-27 | スローン − ケタリング・インスティテュート・フォー・キャンサー・リサーチ | 標識されたｈｓｐ９０阻害剤の使用 |
| CA2905509A1 (en) | 2013-03-15 | 2014-09-18 | Memorial Sloan-Kettering Cancer Center | Hsp90-targeted cardiac imaging and therapy |
| US10071130B2 (en) | 2013-12-12 | 2018-09-11 | The University Of Chicago | Methods and compositions related to Hsp90 inhibitors and breast cancer |
| CN107110869B (zh) | 2014-09-17 | 2021-08-10 | 纪念斯隆-凯特琳癌症中心 | Hsp90-靶向炎症和感染成像及治疗 |
-
2012
- 2012-07-06 JP JP2014520226A patent/JP6054389B2/ja active Active
- 2012-07-06 US US14/131,423 patent/US9555137B2/en active Active
- 2012-07-06 CN CN201280040606.7A patent/CN104081206B/zh not_active Expired - Fee Related
- 2012-07-06 EP EP19202091.5A patent/EP3709022A1/en not_active Withdrawn
- 2012-07-06 AU AU2012282903A patent/AU2012282903A1/en not_active Abandoned
- 2012-07-06 JP JP2014520227A patent/JP6218147B2/ja not_active Expired - Fee Related
- 2012-07-06 AU AU2012282905A patent/AU2012282905B8/en not_active Ceased
- 2012-07-06 CA CA2841069A patent/CA2841069C/en not_active Expired - Fee Related
- 2012-07-06 ES ES12811358.6T patent/ES2624982T3/es active Active
- 2012-07-06 EA EA201490230A patent/EA201490230A1/ru unknown
- 2012-07-06 CA CA2841173A patent/CA2841173C/en not_active Expired - Fee Related
- 2012-07-06 CN CN201810715481.2A patent/CN109374889B/zh active Active
- 2012-07-06 EP EP12811358.6A patent/EP2729806B1/en active Active
- 2012-07-06 KR KR1020177009318A patent/KR102138218B1/ko active IP Right Grant
- 2012-07-06 CN CN201280040632.XA patent/CN104081203B/zh not_active Expired - Fee Related
- 2012-07-06 ES ES17156149T patent/ES2766623T3/es active Active
- 2012-07-06 MX MX2014000286A patent/MX347607B/es active IP Right Grant
- 2012-07-06 WO PCT/US2012/045864 patent/WO2013009657A1/en active Application Filing
- 2012-07-06 DK DK12811358.6T patent/DK2729806T3/en active
- 2012-07-06 EP EP17156149.1A patent/EP3208615B1/en active Active
- 2012-07-06 WO PCT/US2012/045861 patent/WO2013009655A2/en active Application Filing
- 2012-07-06 BR BR112014000445A patent/BR112014000445A2/pt not_active Application Discontinuation
- 2012-07-06 US US14/131,420 patent/US20140294725A1/en not_active Abandoned
- 2012-07-06 KR KR1020147003357A patent/KR102025142B1/ko active IP Right Grant
- 2012-07-06 MX MX2014000292A patent/MX2014000292A/es unknown
-
2014
- 2014-06-12 HK HK18102584.8A patent/HK1243175A1/zh unknown
-
2016
- 2016-11-30 JP JP2016232580A patent/JP6662759B2/ja not_active Expired - Fee Related
-
2017
- 2017-06-27 AU AU2017204369A patent/AU2017204369B2/en not_active Ceased
-
2019
- 2019-07-04 JP JP2019125455A patent/JP2019194232A/ja active Pending
-
2020
- 2020-07-21 US US16/934,881 patent/US11607465B2/en active Active
-
2023
- 2023-01-31 US US18/104,037 patent/US20240058482A1/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1860132A (zh) * | 2003-03-12 | 2006-11-08 | 塔夫兹大学 | 细胞外Hsp90的抑制剂 |
| CN101854955A (zh) * | 2007-09-10 | 2010-10-06 | 马萨诸塞大学 | 靶向线粒体的抗肿瘤剂 |
| WO2010020618A1 (en) * | 2008-08-18 | 2010-02-25 | MAX-PLANCK-Gesellschaft zur Förderung der Wissenschaften e.V. | Susceptibility to hsp90-inhibitors |
Non-Patent Citations (3)
| Title |
|---|
| Antileukemic activity of shepherdin and molecular diversity of hsp90 inhibitors.;Boglarka Gyurkocza等;《Journal of the National Cancer Institute》;20060802;第98卷(第15期);第1068页-1077页 * |
| Regulation of tumor cell mitochondrial homeostasis by an organelle-specific hsp90 chaperone network.;Byoung Heon Kang等;《Cell》;20071019;第131卷;摘要，第259页左侧栏，图5 * |
| Synthesis of purine-scaffold fluorescent probes for heat shock protein 90 with use in flow cytometry and fluorescence microscopy.;Tony Taldone et.al.;《Bioorganic & Medicinal Chemistry Letters》;20110714;第21卷;摘要，第5350页右侧栏-5351页左侧栏 * |
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN104081206B (zh) | 标记的hsp90抑制剂的用途 | |
| Jacobson et al. | Interrogating tumor metabolism and tumor microenvironments using molecular positron emission tomography imaging. Theranostic approaches to improve therapeutics | |
| Huang et al. | The use of PET imaging for prognostic integrin α2β1 phenotyping to detect non-small cell lung cancer and monitor drug resistance responses | |
| Balber et al. | Preclinical in vitro and in vivo evaluation of [18F] FE@ SUPPY for cancer PET imaging: Limitations of a xenograft model for colorectal cancer | |
| Class et al. | Patent application title: USES OF LABELED HSP90 INHIBITORS Inventors: Gabriela Chiosis (New York, NY, US) Gabriela Chiosis (New York, NY, US) Tony Taldone (New York, NY, US) Mary L. Alpaugh (Teaneck, NJ, US) Erica M. Gomes-Dagama (New Rochelle, NY, US) Monica L. Guzman (New York, NY, US) Hongliang Zong (New York, NY, US) Assignees: CORNELL UNIVERSITY SLOAN-KETTERING INSTITUTE FOR CANCER RESEARCH | |
| NZ620634B2 (en) | Uses of labeled hsp90 inhibitors | |
| Korsen | Molecular Imaging and Radioimmunotherapy Targeting Delta-Like Ligand 3 in Neuroendocrine Prostate Cancer |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C53 | Correction of patent of invention or patent application | ||
| CB02 | Change of applicant information |
Address after: American New York Applicant after: SLOAN-KETTERING INSTITUTE FOR CANCER RESEARCH Applicant after: CORNELL University Address before: American New York Applicant before: Sloan-Kettering Institute For Cancer Research Applicant before: Cornell University |
|
| COR | Change of bibliographic data |
Free format text: CORRECT: ADDRESS; FROM: Free format text: CORRECT: APPLICANT; FROM: SLOAN KETTERING INST. OF CANCER RESEARCH TO: SLOAN-KETTERING INSTITUTE FOR CANCER RESEARCH |
|
| GR01 | Patent grant | ||
| GR01 | Patent grant | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20170609 |
|
| CF01 | Termination of patent right due to non-payment of annual fee |